Aortic biological valve thrombosis in an HIV positive patient.

PubMed

Achouh, Paul; Jemel, Amine; Chaudeurge, Aurélie; Redheuil, Alban; Zegdi, Rachid; Fabiani, Jean-Noël

2011-06-01

Biological aortic valve thrombosis is an exceptional complication. A 64-year-old patient positive for human immunodeficiency virus presented for syncope on exertion, 2 years after an aortic bioprosthetic valve replacement and double coronary artery bypass. Transvalvular aortic mean gradient was approximately 50 mm Hg on echocardiogram and catheterization. Cardiac computed tomography scan showed a limited opening of the bioprosthesis cusps. Surgical exploration revealed thrombosis of the three cusps on the aortic side, limiting the opening of the valve. No relation could be established between the patient's human immunodeficiency virus status and valve thrombosis. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Genetics of the extracellular matrix in aortic aneurysmal diseases.

PubMed

Lin, Chien-Jung; Lin, Chieh-Yu; Stitziel, Nathan O

2018-04-12

Aortic aneurysms are morbid conditions that can lead to rupture or dissection and are categorized as thoracic (TAA) or abdominal aortic aneurysms (AAA) depending on their location. While AAA shares overlapping risk factors with atherosclerotic cardiovascular disease, TAA exhibits strong heritability. Human genetic studies in the past two decades have successfully identified numerous genes involved in both familial and sporadic forms of aortic aneurysm. In this review we will discuss the genetic basis of aortic aneurysm, focusing on the extracellular matrix and how insights from these studies have informed our understanding of human biology and disease pathogenesis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease.

PubMed

Watson, Alanna; Nong, Zengxuan; Yin, Hao; O'Neil, Caroline; Fox, Stephanie; Balint, Brittany; Guo, Linrui; Leo, Oberdan; Chu, Michael W A; Gros, Robert; Pickering, J Geoffrey

2017-06-09

The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD + ) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. To determine whether a Nampt-NAD + control system exists within the aortic media and is required for aortic health. Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD + control system in SMCs impacts aortic integrity, mice with Nampt -deficient SMCs were generated. SMC- Nampt knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD + in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD + with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT. NAMPT promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with NAMPT expression. The aortic media depends on an intrinsic NAD + fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy. © 2017 American Heart Association, Inc.

Aortic annulus sizing using watershed transform and morphological approach for CT images

NASA Astrophysics Data System (ADS)

Mohammad, Norhasmira; Omar, Zaid; Sahrim, Mus'ab

2018-02-01

Aortic valve disease occurs due to calcification deposits on the area of leaflets within the human heart. It is progressive over time where it can affect the mechanism of the heart valve. To avoid the risk of surgery for vulnerable patients especially senior citizens, a new method has been introduced: Transcatheter Aortic Valve Implantation (TAVI), which places a synthetic catheter within the patient's valve. This entails a procedure of aortic annulus sizing, which requires manual measurement of the scanned images acquired from Computed Tomographic (CT) by experts. The step requires intensive efforts, though human error may still eventually lead to false measurement. In this research, image processing techniques are implemented onto cardiac CT images to achieve an automated and accurate measurement of the heart annulus. The image is first put through pre-processing for noise filtration and image enhancement. Then, a marker image is computed using the combination of opening and closing operations where the foreground image is marked as a feature while the background image is set to zero. Marker image is used to control the watershed transformation and also to prevent oversegmentation. This transformation has the advantage of fast computational and oversegmentation problems, which usually appear with the watershed transform can be solved with the introduction of marker image. Finally, the measurement of aortic annulus from the image data is obtained through morphological operations. Results affirm the approach's ability to achieve accurate annulus measurements compared to conventional techniques.

Sex, pregnancy and aortic disease in Marfan syndrome.

PubMed

Renard, Marjolijn; Muiño-Mosquera, Laura; Manalo, Elise C; Tufa, Sara; Carlson, Eric J; Keene, Douglas R; De Backer, Julie; Sakai, Lynn Y

2017-01-01

Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown. In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17β-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts. Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17β-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells. Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans.

PubMed

Osman, Narin; Grande-Allen, K Jane; Ballinger, Mandy L; Getachew, Robel; Marasco, Silvana; O'Brien, Kevin D; Little, Peter J

2013-01-01

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-β1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factorβ1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-β1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-β1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease. Diseased human aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-β1 and phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells, Western blots showed that transforming growth factor-β1 stimulated phosphorylation in both the carboxy and linker regions of Smad2/3, which was inhibited by the transforming growth factor-β1 receptor inhibitor SB431542. Gel electrophoresis and size exclusion chromatography demonstrated that SB431542 decreased transforming growth factor-β1-mediated [(35)S]-sulfate incorporation into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived from transforming growth factor-β1-treated valve interstitial cells, gel mobility shift assays demonstrated that inhibition of transforming growth factor-β1 receptor signaling resulted in decreased lipid binding. Classic transforming growth factor-β1 signaling is present in human aortic valves in vivo and contributes to the modification of proteoglycans expressed by valve interstitial cells in vitro. These findings suggest that transforming growth factor-β1 may promote increased low-density lipoprotein binding in the early phases of calcific aortic valve disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review

PubMed Central

Tsamis, Alkiviadis; Krawiec, Jeffrey T.; Vorp, David A.

2013-01-01

Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and ageing-induced stiffening. The microstructure of the aortic tissue has been studied with great interest, because alteration of the quantity and/or architecture of the connective fibres (elastin and collagen) within the aortic wall, which directly imparts elasticity and strength, can lead to the mechanical and functional changes associated with these conditions. This review article summarizes the state of the art with respect to characterization of connective fibre microstructure in the wall of the human aorta in ageing and disease, with emphasis on the ascending thoracic aorta and abdominal aorta where the most common forms of aortic disease tend to occur. PMID:23536538

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta

PubMed Central

Pal, Siladitya; Tsamis, Alkiviadis; Pasta, Salvatore; D'Amore, Antonio; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2014-01-01

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovaular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber microarchitecture, obtained in a parallel study from multi-photon microopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence. PMID:24484644

Association between osteopontin and human abdominal aortic aneurysm.

PubMed

Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

2007-03-01

In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

PubMed

Bi, Yonghua; Chen, Hongmei; Li, Yahua; Yu, Zepeng; Han, Xinwei; Ren, Jianzhuang

2018-01-01

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

PubMed

Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal

2014-01-01

Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

Epigenetic control of vascular smooth muscle cells in Marfan and non-Marfan thoracic aortic aneurysms

PubMed Central

Gomez, Delphine; Coyet, Aurélie; Ollivier, Véronique; Jeunemaitre, Xavier; Jondeau, Guillaume; Michel, Jean-Baptiste; Vranckx, Roger

2011-01-01

Aims Human thoracic aortic aneurysms (TAAs) are characterized by extracellular matrix breakdown associated with progressive smooth muscle cell (SMC) rarefaction. These features are present in all types of TAA: monogenic forms [mainly Marfan syndrome (MFS)], forms associated with bicuspid aortic valve (BAV), and degenerative forms. Initially described in a mouse model of MFS, the transforming growth factor-β1 (TGF-β1)/Smad2 signalling pathway is now assumed to play a role in TAA of various aetiologies. However, the relation between the aetiological diversity and the common cell phenotype with respect to TGF-β signalling remains unexplained. Methods and results This study was performed on human aortic samples, including TAA [MFS, n = 14; BAV, n = 15; and degenerative, n = 19] and normal aortas (n = 10) from which tissue extracts and human SMCs and fibroblasts were obtained. We show that all types of TAA share a complex dysregulation of Smad2 signalling, independent of TGF-β1 in TAA-derived SMCs (pharmacological study, qPCR). The Smad2 dysregulation is characterized by an SMC-specific, heritable activation and overexpression of Smad2, compared with normal aortas. The cell specificity and heritability of this overexpression strongly suggest the implication of epigenetic control of Smad2 expression. By chromatin immunoprecipitation, we demonstrate that the increases in H3K9/14 acetylation and H3K4 methylation are involved in Smad2 overexpression in TAA, in a cell-specific and transcription start site-specific manner. Conclusion Our results demonstrate the heritability, the cell specificity, and the independence with regard to TGF-β1 and genetic backgrounds of the Smad2 dysregulation in human thoracic aneurysms and the involvement of epigenetic mechanisms regulating histone marks in this process. PMID:20829218

Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

PubMed

Spinosa, Michael; Lu, Guanyi; Su, Gang; Bontha, Sai Vineela; Gehrau, Ricardo; Salmon, Morgan D; Smith, Joseph R; Weiss, Mark L; Mas, Valeria R; Upchurch, Gilbert R; Sharma, Ashish K

2018-05-29

The formation of an abdominal aortic aneurysm (AAA) is characterized by inflammation, macrophage infiltration, and vascular remodeling. In this study, we tested the hypothesis that mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) immunomodulate aortic inflammation, to mitigate AAA formation via modulation of microRNA-147. An elastase-treatment model of AAA was used in male C57BL/6 wild-type (WT) mice. Administration of EVs in elastase-treated WT mice caused a significant attenuation of aortic diameter and mitigated proinflammatory cytokines, inflammatory cell infiltration, an increase in smooth muscle cell α-actin expression, and a decrease in elastic fiber disruption, compared with untreated mice. A 10-fold up-regulation of microRNA (miR)-147, a key mediator of macrophage inflammatory responses, was observed in murine aortic tissue in elastase-treated mice compared with controls on d 14. EVs derived from MSCs transfected with miR-147 mimic, but not with miR-147 inhibitor, attenuated aortic diameter, inflammation, and leukocyte infiltration in elastase-treated mice. In vitro studies of human aortic tissue explants and murine-derived CD11b + macrophages induced proinflammatory cytokines after elastase treatment, and the expression was attenuated by cocultures with EVs transfected with miR-147 mimic, but not with miR-147 inhibitor. Thus, our findings define a critical role of MSC-derived EVs in attenuation of aortic inflammation and macrophage activation via miR-147 during AAA formation.-Spinosa, M., Lu, G., Su, G., Bontha, S. V., Gehrau, R., Salmon, M. D., Smith, J. R., Weiss, M. L., Mas, V. R., Upchurch, G. R., Sharma, A. K. Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

Decorin and biglycan retain LDL in disease-prone valvular and aortic subendothelial intimal matrix

PubMed Central

Neufeld, Edward B.; Zadrozny, Leah M.; Phillips, Darci; Aponte, Angel; Yu, Zu-Xi; Balaban, Robert S.

2014-01-01

Objective Subendothelial LDL retention by intimal matrix proteoglycans is an initial step in atherosclerosis and calcific aortic valve disease. Herein, we identify decorin and biglycan as the proteoglycans that preferentially retain LDL in intimal matrix at disease-prone sites in normal valve and vessel wall. Methods The porcine aortic valve and renal artery ostial diverter, initiation sites of calcific valve disease and renal atherosclerosis, respectively, from normal non-diseased animals were used as models in these studies. Results Fluorescent human LDL was selectively retained on the lesion-prone collagen/proteoglycan-enriched aortic surface of the valve, where the elastic lamina is depleted, as previously observed in lesion-prone sites in the renal ostium. iTRAQ mass spectrometry of valve and diverter protein extracts identified decorin and biglycan as the major subendothelial intimal matrix proteoglycans electrostatically retained on human LDL affinity columns. Decorin levels correlated with LDL binding in lesion-prone sites in both tissues. Collagen binding to LDL was shown to be proteoglycan-mediated. All known basement membrane proteoglycans bound LDL suggesting they may modulate LDL uptake into the subendothelial matrix. The association of purified decorin with human LDL in an in vitro microassay was blocked by serum albumin and heparin suggesting anti-atherogenic roles for these proteins in vivo. Conclusions LDL electrostatic interactions with decorin and biglycan in the valve leaflets and vascular wall is a major source of LDL retention. The complementary electrostatic sites on LDL or these proteoglycans may provide a novel therapeutic target for preventing one of the earliest events in these cardiovascular diseases. PMID:24529131

Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata

PubMed Central

Brokopp, Chad E.; Schoenauer, Roman; Richards, Peter; Bauer, Stefan; Lohmann, Christine; Emmert, Maximilian Y.; Weber, Benedikt; Winnik, Stephan; Aikawa, Elena; Graves, Kirk; Genoni, Michele; Vogt, Peter; Lüscher, Thomas F.; Renner, Christoph; Hoerstrup, Simon P.; Matter, Christian M.

2011-01-01

Aims Collagen degradation in atherosclerotic plaques with thin fibrous caps renders them more prone to rupture. Fibroblast activation protein (FAP) plays a role in arthritis and tumour formation through its collagenase activity. However, the significance of FAP in thin-cap human fibroatheromata remains unknown. Methods and results We detected enhanced FAP expression in type IV–V human aortic atheromata (n = 12), compared with type II–III lesions (n = 9; P < 0.01) and healthy aortae (n = 8; P < 0.01) by immunostaining and western blot analyses. Fibroblast activation protein was also increased in thin-cap (<65 µm) vs. thick-cap (≥65 µm) human coronary fibroatheromata (n = 12; P < 0.01). Fibroblast activation protein was expressed by human aortic smooth muscle cells (HASMC) as shown by colocalization on immunofluorescent aortic plaque stainings (n = 10; P < 0.01) and by flow cytometry in cell culture. Although macrophages did not express FAP, macrophage burden in human aortic plaques correlated with FAP expression (n = 12; R2= 0.763; P < 0.05). Enzyme-linked immunosorbent assays showed a time- and dose-dependent up-regulation of FAP in response to human tumour necrosis factor α (TNFα) in HASMC (n = 6; P < 0.01). Moreover, supernatants from peripheral blood-derived macrophages induced FAP expression in cultured HASMC (n = 6; P < 0.01), an effect abolished by blocking TNFα (n = 6; P < 0.01). Fibroblast activation protein associated with collagen-poor regions in human coronary fibrous caps and digested type I collagen and gelatin in vitro (n = 6; P < 0.01). Zymography revealed that FAP-mediated collagenase activity was neutralized by an antibody directed against the FAP catalytic domain both in HASMC (n = 6; P < 0.01) and in fibrous caps of atherosclerotic plaques (n = 10; P < 0.01). Conclusion Fibroblast activation protein expression in HASMC is induced by macrophage-derived TNFα. Fibroblast activation protein associates with thin-cap human coronary fibroatheromata and contributes to type I collagen breakdown in fibrous caps. PMID:21292680

Detection of Hydroxyapatite in Calcified Cardiovascular Tissues

PubMed Central

Lee, Jae Sam; Morrisett, Joel D.; Tung, Ching-Hsuan

2012-01-01

Objective The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. Methods A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Results Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Conclusion Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. PMID:22877867

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

PubMed Central

Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T.; Öörni, Katariina

2013-01-01

In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine –ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis. PMID:23762432

Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

NASA Astrophysics Data System (ADS)

Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

2017-06-01

Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular treatment of AAA.

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Validity of the Water Hammer Formula for Determining Regional Aortic Pulse Wave Velocity: Comparison of One-Point and Two-Point (Foot-to-Foot) Measurements Using a Multisensor Catheter in Human

PubMed Central

2013-01-01

Background: Lack of high-fidelity simultaneous measurements of pressure and flow velocity in the aorta has impeded the direct validation of the water-hammer formula for estimating regional aortic pulse wave velocity (AO-PWV1) and has restricted the study of the change of beat-to-beat AO-PWV1 under varying physiological conditions in man. Methods: Aortic pulse wave velocity was derived using two methods in 15 normotensive subjects: 1) the conventional two-point (foot-to-foot) method (AO-PWV2) and 2) a one-point method (AO-PWV1) in which the pressure velocity-loop (PV-loop) was analyzed based on the water hammer formula using simultaneous measurements of flow velocity (Vm) and pressure (Pm) at the same site in the proximal aorta using a multisensor catheter. AO-PWV1 was calculated from the slope of the linear regression line between Pm and Vm where wave reflection (Pb) was at a minimum in early systole in the PV-loop using the water hammer formula, PWV1 = (Pm/Vm)/ρ, where ρ is the blood density. AO-PWV2 was calculated using the conventional two-point measurement method as the distance/traveling time of the wave between 2 sites for measuring P in the proximal aorta. Beat-to-beat alterations of AO-PWV1 in relationship to aortic pressure and linearity of the initial part of the PV-loop during a Valsalva maneuver were also assessed in one subject. Results: The initial part of the loop became steeper in association with the beat-to-beat increase in diastolic pressure in phase 4 during the Valsalva maneuver. The linearity of the initial part of the PV-loop was maintained consistently during the maneuver. Flow velocity vs. pressure in the proximal aorta was highly linear during early systole, with Pearson’s coefficients ranging from 0.9954 to 0.9998. The average values of AO-PWV1 and AO-PWV2 were 6.3 ± 1.2 and 6.7 ± 1.3 m/s, respectively. The regression line of AO-PWV1 on AO-PWV2 was y = 0.95x + 0.68 (r = 0.93, p <0.001). Conclusion: This study concluded that the water-hammer formula (one-point method) provides a reliable and conventional estimate of beat-to-beat aortic regional pulse wave velocity consistently regardless of the changes in physiological states in human clinically. (*English Translation of J Jpn Coll Angiol 2011; 51: 215-221) PMID:23825494

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

NASA Technical Reports Server (NTRS)

Smith, M. L.; Beightol, L. A.; Fritsch-Yelle, J. M.; Ellenbogen, K. A.; Porter, T. R.; Eckberg, D. L.

1996-01-01

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells

PubMed Central

Huang, Peixin; Riordan, Sean M.; Heruth, Daniel P.; Grigoryev, Dmitry N.; Zhang, Li Qin; Ye, Shui Qing

2015-01-01

Aging is the predominant risk factor for cardiovascular diseases and contributes to a considerably more severe outcome in patients with acute myocardial infarction. Resveratrol, a polyphenol found in red wine, is a caloric restriction mimetic with potential anti-aging properties which has emerged as a beneficial nutraceutical for patients with cardiovascular disease. Although resveratrol is widely consumed as a nutritional supplement, its mechanism of action remains to be elucidated fully. Here, we report that resveratrol activates human nicotinamide phosphoribosyltransferase (NAMPT), SIRT4 and telomerase reverse transcriptase (hTERT) in human aortic smooth muscle cells. Similar observations were obtained in resveratrol treated C57BL/6J mouse heart and liver tissues. Resverotrol can also augment telomerase activity in both human pulmonary microvascular endothelial cells and A549 cells. Blocking NAMPT and SIRT4 expression prevents induction of hTERT in human aortic smooth muscle cells while overexpression of NAMPT elevates the telomerase activity induced by resveratrol in A549 cells. Together, these results identify a NAMPT-SIRT4-hTERT axis as a novel mechanism by which resveratrol may affect the anti-aging process in human aortic smooth muscle cells, mouse hearts and other cells. These findings enrich our understanding of the positive effects of resveratrol in human cardiovascular diseases. PMID:25926556

The use of a stentless porcine bioprosthesis to repair an ascending aortic aneurysm in combination with aortic valve regurgitation.

PubMed Central

Akpinar, B; Sanisoğlu, I; Konuralp, C; Akay, H; Güden, M; Sönmez, B

1999-01-01

Over the years, many surgical methods have evolved for the treatment of ascending aortic aneurysm in combination with aortic valve regurgitation; however, precise guidelines for optimal surgical techniques for varying presentations have not been defined. We describe the use of a stentless porcine bioprosthesis (Medtronic Freestyle) in a patient with an ascending aortic aneurysm and aortic regurgitation. We used the complete root replacement method, and anastomosed a Dacron graft (Hemashield) between the bioprosthetic valve and the native aorta to replace the distal part of the aneurysm. Images PMID:10524742

The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.

PubMed

Wojakowski, W; Gminski, J; Siemianowicz, K; Goss, M; Machalski, M

2001-03-01

Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.

Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

PubMed

Nelson, G N; Roh, J D; Mirensky, T L; Wang, Y; Yi, T; Tellides, G; Pober, J S; Shkarin, P; Shapiro, E M; Saltzman, W M; Papademetris, X; Fahmy, T M; Breuer, C K

2008-11-01

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

Validity of the Water Hammer Formula for Determining Regional Aortic Pulse Wave Velocity: Comparison of One-Point and Two-Point (Foot-to-Foot) Measurements Using a Multisensor Catheter in Human.

PubMed

Hanya, Shizuo

2013-01-01

Lack of high-fidelity simultaneous measurements of pressure and flow velocity in the aorta has impeded the direct validation of the water-hammer formula for estimating regional aortic pulse wave velocity (AO-PWV1) and has restricted the study of the change of beat-to-beat AO-PWV1 under varying physiological conditions in man. Aortic pulse wave velocity was derived using two methods in 15 normotensive subjects: 1) the conventional two-point (foot-to-foot) method (AO-PWV2) and 2) a one-point method (AO-PWV1) in which the pressure velocity-loop (PV-loop) was analyzed based on the water hammer formula using simultaneous measurements of flow velocity (Vm) and pressure (Pm) at the same site in the proximal aorta using a multisensor catheter. AO-PWV1 was calculated from the slope of the linear regression line between Pm and Vm where wave reflection (Pb) was at a minimum in early systole in the PV-loop using the water hammer formula, PWV1 = (Pm/Vm)/ρ, where ρ is the blood density. AO-PWV2 was calculated using the conventional two-point measurement method as the distance/traveling time of the wave between 2 sites for measuring P in the proximal aorta. Beat-to-beat alterations of AO-PWV1 in relationship to aortic pressure and linearity of the initial part of the PV-loop during a Valsalva maneuver were also assessed in one subject. The initial part of the loop became steeper in association with the beat-to-beat increase in diastolic pressure in phase 4 during the Valsalva maneuver. The linearity of the initial part of the PV-loop was maintained consistently during the maneuver. Flow velocity vs. pressure in the proximal aorta was highly linear during early systole, with Pearson's coefficients ranging from 0.9954 to 0.9998. The average values of AO-PWV1 and AO-PWV2 were 6.3 ± 1.2 and 6.7 ± 1.3 m/s, respectively. The regression line of AO-PWV1 on AO-PWV2 was y = 0.95x + 0.68 (r = 0.93, p <0.001). This study concluded that the water-hammer formula (one-point method) provides a reliable and conventional estimate of beat-to-beat aortic regional pulse wave velocity consistently regardless of the changes in physiological states in human clinically. (English Translation of J Jpn Coll Angiol 2011; 51: 215-221).

A novel sax-stent method in treatment of ascending aorta and aortic arch aneurysms evaluated by finite element simulations.

PubMed

Arokiaraj, M C; De Beule, M; De Santis, G

2017-02-01

A novel stent method to simplify treatment of proximal ascending aorta and aortic arch aneurysms was developed and investigated by finite element analysis. Therapy of ascending aortic and aortic arch aneurysms is difficult and challenging and is associated with various complications. A 55mm wide×120mm long stent was designed without the stent graft and the stent was deployed by an endovascular method in a virtual patient-specific aneurysm model. The stress-strain analysis and deployment characteristics were performed in a finite element analysis using the Abaqus software. The stent, when embedded in the aortic wall, significantly reduced aortic wall stresses, while preserving the side coronary ostia and side branches in the aortic arch. When tissue growth was modeled computationally over the stent struts the wall stresses in aorta was reduced. This effect became more pronounced when increasing the thickness of the tissue growth. There were no abnormal stresses in the aorta, coronary ostium and at the origin of aortic branches. The stent reduced aneurysm expansion cause by hypertensive condition from 2mm without stenting to 1.3mm after stenting and embedding. In summary, we uncovered a simple treatment method using a bare nitinol stent without stent graft in the treatment of the proximal aorta and aortic arch aneurysms, which could eventually replace the complex treatment methods for this disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells.

PubMed

Tsai, J C; Jain, M; Hsieh, C M; Lee, W S; Yoshizumi, M; Patterson, C; Perrella, M A; Cooke, C; Wang, H; Haber, E; Schlegel, R; Lee, M E

1996-02-16

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.

Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall

PubMed Central

Guri, Amir J.; Misyak, Sarah A.; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2009-01-01

Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which abscisic acid (ABA) prevents or ameliorates atherosclerosis. Apolipoprotein E-deficient (ApoE −/−) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on days 0, 28, 56, and 72. Gene expression, immune cell infiltration, and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3’, 5’-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80+CD11b+ macrophages and CD4+ T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and upregulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall, and upregulates aortic eNOS expression in ApoE−/− mice. PMID:20092994

Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall.

PubMed

Guri, Amir J; Misyak, Sarah A; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2010-12-01

Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which ABA prevents or ameliorates atherosclerosis. apolipoprotein E-deficient (ApoE(-/-)) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on Days 0, 28, 56 and 72. Gene expression, immune cell infiltration and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3',5'-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80(+)CD11b(+) macrophages and CD4(+) T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and up-regulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall and up-regulates aortic eNOS expression in ApoE(-/-) mice. Copyright © 2010 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fetterly, K; Mathew, V

Purpose: Transcatheter aortic valve replacement (TAVR) procedures provide a method to implant a prosthetic aortic valve via a minimallyinvasive, catheter-based procedure. TAVR procedures require use of interventional fluoroscopy c-arm projection angles which are aligned with the aortic valve plane to minimize prosthetic valve positioning error due to x-ray imaging parallax. The purpose of this work is to calculate the continuous range of interventional fluoroscopy c-arm projection angles which are aligned with the aortic valve plane from a single planar image of a valvuloplasty balloon inflated across the aortic valve. Methods: Computational methods to measure the 3D angular orientation of themore » aortic valve were developed. Required inputs include a planar x-ray image of a known valvuloplasty balloon inflated across the aortic valve and specifications of x-ray imaging geometry from the DICOM header of the image. A-priori knowledge of the species-specific typical range of aortic orientation is required to specify the sign of the angle of the long axis of the balloon with respect to the x-ray beam. The methods were validated ex-vivo and in a live pig. Results: Ex-vivo experiments demonstrated that the angular orientation of a stationary inflated valvuloplasty balloon can be measured with precision less than 1 degree. In-vivo pig experiments demonstrated that cardiac motion contributed to measurement variability, with precision less than 3 degrees. Error in specification of x-ray geometry directly influences measurement accuracy. Conclusion: This work demonstrates that the 3D angular orientation of the aortic valve can be calculated precisely from a planar image of a valvuloplasty balloon inflated across the aortic valve and known x-ray geometry. This method could be used to determine appropriate c-arm angular projections during TAVR procedures to minimize x-ray imaging parallax and thereby minimize prosthetic valve positioning errors.« less

The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells

PubMed Central

Patel, Vishal; Carrion, Katrina; Hollands, Andrew; Hinton, Andrew; Gallegos, Thomas; Dyo, Jeffrey; Sasik, Roman; Leire, Emma; Hardiman, Gary; Mohamed, Salah A.; Nigam, Sanjay; King, Charles C.; Nizet, Victor; Nigam, Vishal

2015-01-01

Bicuspid aortic valves calcify at a significantly higher rate than normal aortic valves, a process that involves increased inflammation. Because we have previously found that bicuspid aortic valve experience greater stretch, we investigated the potential connection between stretch and inflammation in human aortic valve interstitial cells (AVICs). Microarray, quantitative PCR (qPCR), and protein assays performed on AVICs exposed to cyclic stretch showed that stretch was sufficient to increase expression of interleukin and metalloproteinase family members by more than 1.5-fold. Conditioned medium from stretched AVICs was sufficient to activate leukocytes. microRNA sequencing and qPCR experiments demonstrated that miR-148a-3p was repressed in both stretched AVICs (43% repression) and, as a clinical correlate, human bicuspid aortic valves (63% reduction). miR-148a-3p was found to be a novel repressor of IKBKB based on data from qPCR, luciferase, and Western blot experiments. Furthermore, increasing miR-148a-3p levels in AVICs was sufficient to decrease NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and NF-κB target gene expression. Our data demonstrate that stretch-mediated activation of inflammatory pathways is at least partly the result of stretch-repression of miR-148a-3p and a consequent failure to repress IKBKB. To our knowledge, we are the first to report that cyclic stretch of human AVICs activates inflammatory genes in a tissue-autonomous manner via a microRNA that regulates a central inflammatory pathway.—Patel, V., Carrion, K., Hollands, A., Hinton, A., Gallegos, T., Dyo, J., Sasik, R., Leire, E., Hardiman, G., Mohamed, S. A., Nigam, S., King, C. C., Nizet, V., Nigam V. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells. PMID:25630970

Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome.

PubMed

Wanga, Shaynah; Hibender, Stijntje; Ridwan, Yanto; van Roomen, Cindy; Vos, Mariska; van der Made, Ingeborg; van Vliet, Nicole; Franken, Romy; van Riel, Luigi Amjg; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara Jm; de Vries, Carlie Jm; Essers, Jeroen; de Waard, Vivian

2017-11-01

Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1 C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild-type SMCs. The elastin peptide-induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen-activated protein kinase kinase-1/2 inhibitor, indicating downstream involvement of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near-infrared fluorescent bisphosphonate probe OsteoSense-800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co-localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin-derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation and thus predict aortic events in MFS patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Detection of hydroxyapatite in calcified cardiovascular tissues.

PubMed

Lee, Jae Sam; Morrisett, Joel D; Tung, Ching-Hsuan

2012-10-01

The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

PubMed

Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru

2015-06-01

Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. © 2015 American Heart Association, Inc.

Outcomes After Operations for Unicuspid Aortic Valve With or Without Ascending Repair in Adults

PubMed Central

Zhu, Yuanjia; Roselli, Eric E.; Idrees, Jay J.; Wojnarski, Charles M.; Griffin, Brian; Kalahasti, Vidyasagar; Pettersson, Gosta; Svensson, Lars G.

2016-01-01

Background Unicuspid aortic valve is an important subset of bicuspid aortic valve, and knowledge regarding its aortopathy pattern and surgical outcomes is limited. Our objectives were to characterize unicuspid aortic valve patients, associated aortopathy, and surgical outcomes. Methods From January 1990 to May 2013, 149 adult unicuspid aortic valve patients underwent aortic valve replacement or repair for aortic stenosis (n = 13), regurgitation (n = 13), or both (n = 123), and in 91 (61%) the aortic valve operation was combined with aortic repair. Data were obtained from the Cardiovascular Information Registry and medical record review. Three-dimensional imaging analysis was performed from preoperative computed tomography and magnetic resonance imaging scans. The Kaplan-Meier method was used for survival analysis. Results Patients had a mean maximum aortic diameter of 44 ± 8 mm and variably involved the aortic root, ascending, or arch, or both. Patients with valve operations alone were more likely to be hypertensive (p = 0.01) and to have severe aortic stenosis (p = 0.07) than those who underwent concurrent aortic operations. There were no operative deaths, strokes, or myocardial infarctions. Patients undergoing aortic repair had better long-term survival. Estimated survival at 1, 5, and 10 years was 100%, 100%, and 100% after combined operations and was 100%, 88%, and 88% after valve operations alone (p = 0.01). Conclusions Patients with a dysfunctional unicuspid aortic valve frequently present with an ascending aneurysm that requires repair. Combined aortic valve operations and aortic repair was associated with significantly better long-term survival than a valve operation alone. Further study of this association may direct decisions about timing of surgical intervention. PMID:26453423

Evaluation of aortic contractility based on analysis of CT images of the heart

NASA Astrophysics Data System (ADS)

DzierŻak, RóŻa; Maciejewski, Ryszard; Uhlig, Sebastian

2017-08-01

The paper presents a method to assess the aortic contractility based on the analysis of CT images of the heart. This is an alternative method that can be used for patients who cannot be examined by using echocardiography. Usage of medical imaging application for DICOM file processing allows to evaluate the aortic cross section during systole and diastole. It makes possible to assess the level of aortic contractility.

MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1.

PubMed

Tang, Yangfeng; Yu, Shangyi; Liu, Yang; Zhang, Jiajun; Han, Lin; Xu, Zhiyun

2017-09-01

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically downregulated in the aortic media of clinical specimens of the dissected aorta and correlated with molecular markers of the contractile VSMC phenotype. Overexpression of miR-124 by mimicking transfection significantly attenuated platelet-derived growth factor-BB-induced human aortic VSMC proliferation and phenotypic switch. Furthermore, we identified specificity protein 1 (Sp1) as the downstream target of miR-124. A luciferase reporter assay was used to confirm direct miR-124 targeting of the 3'-untranslated region of the Sp1 gene and repression of Sp1 expression in human aortic VSMCs. Furthermore, constitutively active Sp1 in miR-124-overexpressing VSMCs reversed the antiproliferative effects of miR-124. These results demonstrated a novel mechanism of miR-124 modulation of VSMC phenotypic switch by targeting Sp1 expression. NEW & NOTEWORTHY Previous studies have demonstrated that miR-124 is involved in the proliferation of a variety of cell types. However, miRNAs are expressed in a tissue-specific manner. We first identified miR-124 as a critical regulator in human aortic vascular smooth muscle cell differentiation, proliferation, and phenotype switch by targeting the 3'-untranslated region of specificity protein 1. Copyright © 2017 the American Physiological Society.

Animal models in the research of abdominal aortic aneurysms development.

PubMed

Patelis, N; Moris, D; Schizas, D; Damaskos, C; Perrea, D; Bakoyiannis, C; Liakakos, T; Georgopoulos, S

2017-12-20

Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms "animal" or "animal model(s)" and keywords "research", "aneurysm(s)", "aorta", "pancreatic elastase", "Angiotensin", "AngII" "calcium chloride" or "CaCl(2)". Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty and Cassis (2004). We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960's. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are in line with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.

Estimation of cardiac reserve by peak power: validation and initial application of a simplified index

NASA Technical Reports Server (NTRS)

Armstrong, G. P.; Carlier, S. G.; Fukamachi, K.; Thomas, J. D.; Marwick, T. H.

1999-01-01

OBJECTIVES: To validate a simplified estimate of peak power (SPP) against true (invasively measured) peak instantaneous power (TPP), to assess the feasibility of measuring SPP during exercise and to correlate this with functional capacity. DESIGN: Development of a simplified method of measurement and observational study. SETTING: Tertiary referral centre for cardiothoracic disease. SUBJECTS: For validation of SPP with TPP, seven normal dogs and four dogs with dilated cardiomyopathy were studied. To assess feasibility and clinical significance in humans, 40 subjects were studied (26 patients; 14 normal controls). METHODS: In the animal validation study, TPP was derived from ascending aortic pressure and flow probe, and from Doppler measurements of flow. SPP, calculated using the different flow measures, was compared with peak instantaneous power under different loading conditions. For the assessment in humans, SPP was measured at rest and during maximum exercise. Peak aortic flow was measured with transthoracic continuous wave Doppler, and systolic and diastolic blood pressures were derived from brachial sphygmomanometry. The difference between exercise and rest simplified peak power (Delta SPP) was compared with maximum oxygen uptake (VO(2)max), measured from expired gas analysis. RESULTS: SPP estimates using peak flow measures correlated well with true peak instantaneous power (r = 0.89 to 0.97), despite marked changes in systemic pressure and flow induced by manipulation of loading conditions. In the human study, VO(2)max correlated with Delta SPP (r = 0.78) better than Delta ejection fraction (r = 0.18) and Delta rate-pressure product (r = 0.59). CONCLUSIONS: The simple product of mean arterial pressure and peak aortic flow (simplified peak power, SPP) correlates with peak instantaneous power over a range of loading conditions in dogs. In humans, it can be estimated during exercise echocardiography, and correlates with maximum oxygen uptake better than ejection fraction or rate-pressure product.

Patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement. Experimental study.

PubMed

Manouguian, S; Abu-Aishah, N; Neitzel, J

1979-09-01

The experimental results of patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement are reported. The operative technique of this new surgical method is described and the indications are discussed.

Doppler-guided retrograde catheterization system

NASA Astrophysics Data System (ADS)

Frazin, Leon J.; Vonesh, Michael J.; Chandran, Krishnan B.; Khasho, Fouad; Lanza, George M.; Talano, James V.; McPherson, David D.

1991-05-01

The purpose of this study was to investigate a Doppler guided catheterization system as an adjunctive or alternative methodology to overcome the disadvantages of left heart catheterization and angiography. These disadvantages include the biological effects of radiation and the toxic and volume effects of iodine contrast. Doppler retrograde guidance uses a 20 MHz circular pulsed Doppler crystal incorporated into the tip of a triple lumen multipurpose catheter and is advanced retrogradely using the directional flow information provided by the Doppler waveform. The velocity detection limits are either 1 m/second or 4 m/second depending upon the instrumentation. In a physiologic flow model of the human aortic arch, multiple data points revealed a positive wave form when flow was traveling toward the catheter tip indicating proper alignment for retrograde advancement. There was a negative wave form when flow was traveling away from the catheter tip if the catheter was in a branch or bent upon itself indicating improper catheter tip position for retrograde advancement. In a series of six dogs, the catheter was able to be accurately advanced from the femoral artery to the left ventricular chamber under Doppler signal guidance without the use of x-ray. The potential applications of a Doppler guided retrograde catheterization system include decreasing time requirements and allowing safer catheter guidance in patients with atherosclerotic vascular disease and suspected aortic dissection. The Doppler system may allow left ventricular pressure monitoring in the intensive care unit without the need for x-ray and it may allow left sided contrast echocardiography. With pulse velocity detection limits of 4 m/second, this system may allow catheter direction and passage into the aortic root and left ventricle in patients with aortic stenosis. A modification of the Doppler catheter may include transponder technology which would allow precise catheter tip localization once the catheter tip is placed in the aortic root. Such technology may conceivably assist in allowing selective coronary catheterization. These studies have demonstrated that Doppler guided retrograde catheterization provides an accurate method to catheterization the aortic root and left ventricular chamber without x-ray. In humans, it may prove useful in a variety of settings including the development of invasive ultrasonic diagnostic and therapeutic technology.

Properties of calcium-containing microparticles formed in the process of biomineralization of the human aortic wall

NASA Astrophysics Data System (ADS)

Zlatoustova, O. Yu; Vasilev, S. V.; Rudy, A. S.

2016-08-01

The results of the study of human aortic walls, subjected to different stages of mineralization are presented. By means of scanning electron microscopy and X-ray microanalysis the morphology, elemental composition and characteristics of the mineral component localization were investigated. The key differences in the initial, intermediate and final stages of pathological mineralization of the aorta wall were identified. The data obtained may be useful in describing the mechanism of biomineral deposits formation in human body.

Transcatheter Aortic Valve Implantation: Experience with the CoreValve Device.

PubMed

Asgar, Anita W; Bonan, Raoul

2012-01-01

The field of transcatheter aortic valve implantation has been rapidly evolving. The Medtronic CoreValve first emerged on the landscape in 2004 with initial first human studies, and it is currently being studied in the Pivotal US trial. This article details the current experience with the self-expanding aortic valve with a focus on clinical results and ongoing challenges. Copyright © 2012 Elsevier Inc. All rights reserved.

[Clinical analysis of different root treatment methods in acute Stanford type A aortic dissection].

PubMed

Xue, Y X; Zhou, Q; Pan, J; Wang, Q; Cao, H L; Fan, F D; Wang, D J

2017-04-01

Objective: To discuss the perioperative and follow-up results of different surgical methods for acute Stanford type A aortic dissection patients and analyzed the results. Methods: The clinic data of 351 acute Stanford type A aortic dissection patients received surgical therapy at Department of Thoracic and Cardiovascular Surgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital from January 2008 to December 2015 were analyzed retrospectively. There were 272 male and 79 female patients, aging from 22 to 83 years with a mean age of (52±13) years. According to root size, aortic valve structure and the status of dissection involvement, these patients were devided into three major groups: 218 cases with root reconstruction using Dacron felts, 34 cases with root reconstruction concomitant with aortic valve resuspension repair and 99 cases in with Bentall procedure. Proper shape based on the status of dissection involvement of Dacron patch was cut and put between the middle and outerlayer of aorta, then inside the inner layerone band Dacron felt was sutured with the aorta and the new middle layer with Dacron patch as mentioned above. In some cases the prolapsed aortic valve was re-suspended to the aortic cusp. Clinical outcomes among the 3 procedures were compared by χ(2) test, Fisher's exact test, t test and analysis of variance. Results: Cardiopulmonary bypass, cross-clamp, and circulatory arrest times of all the patients were (250±78), (171±70) and (31±10) minutes, respectively. The 30-day mortality was 9.2%(33/351), while no difference among the 3 procedures (9.6%, 8.8% and 9.1%). In the average follow-up time of (26.0±23.0) months (range from 0.5 to 90.0 months), survival rates were similar among the 3 procedures (77.7%, 77.4% and 77.8%). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (diameter of 50 mm). Conclusions: The indication of root management of acute Stanford type A aortic dissection is based on the diameter of aortic root, structure of aortic leaflets, and the dissection involvement. For most acute Stanford type A aortic dissection patients, aortic root reconstruction is a feasible and safe method.

Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis

PubMed Central

Dilu, VP; George, Raju

2017-01-01

Introduction An integrated approach that incorporates two dimensional, M mode and Doppler echocardiographic evaluation has become the standard means for accurate quantification of severity of valvular aortic stenosis. Maximal separation of the aortic valve cusps during systole has been shown to correlate well with the severity of aortic stenosis measured by other echocardiographic parameters. Aim To study the correlation between Maximal Aortic valve Cusp Separation (MACS) and severity of aortic valve stenosis and to find cut-off values of MACS for detecting severe and mild aortic stenosis. Materials and Methods In the present prospective observational study, we have compared the accuracy of MACS distance and the aortic valve area calculated by continuity equation in 59 patients with varying degrees of aortic valve stenosis. Aortic leaflet separation in M mode was identified as the distance between the inner edges of the tips of these structures at mid systole in the parasternal long axis view. Cuspal separation was also measured in 2D echocardiography from the parasternal long axis view and the average of the two values was taken as the MACS. Patients were grouped into mild, moderate and severe aortic stenosis based on the aortic valve area calculated by continuity equation. The resultant data regarding maximal leaflet separation on cross-sectional echocardiogram was then subjected to linear regression analysis in regard to correlation with the peak transvalvular aortic gradient as well as the calculated aortic valve area. A cut-off value for each group was derived using ROC curve. Results There was a strong correlation between MACS and aortic valve area measured by continuity equation and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis, with high sensitivity, specificity and positive predictive value. MACS above 11.25 mm practically ruled out significant aortic stenosis. Conclusion Measurement of MACS is a simple echocardio-graphic method to assess the severity of valvular aortic stenosis, with high sensitivity and specificity. MACS can be extremely useful in two clinical situations as a simple screening tool for assessment of stenosis severity and also helps in decision making non invasively when there is discordance between the other echocardiographic parameters of severity of aortic stenosis. PMID:28764221

Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice.

PubMed

Gioscia-Ryan, Rachel A; Battson, Micah L; Cuevas, Lauren M; Eng, Jason S; Murphy, Michael P; Seals, Douglas R

2018-05-01

Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes-including collagen overabundance and elastin degradation-and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders.

Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice

PubMed Central

Gioscia-Ryan, Rachel A.; Battson, Micah L.; Cuevas, Lauren M.; Eng, Jason S.; Murphy, Michael P.

2018-01-01

Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes—including collagen overabundance and elastin degradation—and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders. PMID:29074712

Human cytomegalovirus immediate early protein 2 enhances myocardin-mediated survival of rat aortic smooth muscle cells.

PubMed

Liao, Xing-Hua; Dong, Xiumei; Wu, Chenyu; Wang, Tao; Liu, Fenyong; Zhou, Jun; Zhang, Tong-Cun

2014-11-04

Human cytomegalovirus (HCMV) may increase the incidence of restenosis and predispose to atherosclerosis. The lesions of restenosis and atherosclerosis often contain smooth muscle cells (SMCs) with high rates of proliferation and apoptosis. One of the immediate early (IE) gene products of HCMV-IE2 affects transcriptional activities of some cellular factors in SMCs, including myocardin. In this study, we studied the effects of IE2 and myocardin on PI3K pathway inducer wortmannin induced apoptosis in rat aortic SMCs. We show that the transcriptional activity of myocardin on Mcl-1 promoter is enhanced by co-expression of HCMV IE2 in rat aortic SMCs; and the expressions of mRNA and protein of antiapoptotic genes-Mcl-1 and Bcl-2 are upregulated by IE2 alone and co-transfection of myocardin and IE2, but decreased by myocardin-specific shRNA in rat aortic SMCs. We further demonstrate that co-expression of myocardin and HCMV IE2 declines apoptotic cell numbers and caspase-3 activities induced by serum starvation plus wortmannin in rat aortic SMCs. The results suggest that HCMV IE2 enhances myocardin-mediated survival of rat aortic SMCs under serum deprivation and PI3-kinase inhibition, partly via activation of Mcl-1's antiapoptosis effect. Our study connects HCMV IE2 to myocardin-induced transcriptional program for rat aortic SMCs survival and proliferation, involving in HCMV related restenosis and atherosclerosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Bioactive antibiotic levels in the human aorta.

PubMed

Mutch, D; Richards, G; Brown, R A; Mulder, D S

1982-12-01

A new bioassay was used to determine the level of active antibiotic within the aortic wall in 24 patients undergoing elective aortic surgery involving prosthetic grafts. The patients were divided into three groups and received either cefazolin, clindamycin, or cefoxitin intravenously at the induction of general anesthesia. Cefazolin and cefoxitin attained satisfactory tissue levels. Clindamycin did not reach therapeutic levels in the aortic wall. Blood levels did not correlate well with tissue levels.

Human aortic allograft: an excellent conduit choice for superior vena cava reconstruction

PubMed Central

2014-01-01

Superior vena cava (SVC) reconstruction is occasionally required in the treatment of benign and malignant conditions. We report a patient with symptomatic SVC obstruction secondary to mediastinal fibrosis successfully reconstructed with an aortic allograft. PMID:24428914

A case report and literature overview: Abiotrophia defectiva aortic valve endocarditis in developing countries.

PubMed

Ramos, J N; dos Santos, L S; Vidal, L M R; Pereira, P M A; Salgado, A A; Fortes, C Q; Vieira, V V; Mattos-Guaraldi, A L; Júnior, R H; Damasco, P V

2014-06-01

A fatal case of aortic valve endocarditis due to Abiotrophia defectiva was reported in Brazil. An overview of cases of endocarditis and other human infections related to A. defectiva in developing countries was also accomplished.

Estimation of aortic valve leaflets from 3D CT images using local shape dictionaries and linear coding

NASA Astrophysics Data System (ADS)

Liang, Liang; Martin, Caitlin; Wang, Qian; Sun, Wei; Duncan, James

2016-03-01

Aortic valve (AV) disease is a significant cause of morbidity and mortality. The preferred treatment modality for severe AV disease is surgical resection and replacement of the native valve with either a mechanical or tissue prosthetic. In order to develop effective and long-lasting treatment methods, computational analyses, e.g., structural finite element (FE) and computational fluid dynamic simulations, are very effective for studying valve biomechanics. These computational analyses are based on mesh models of the aortic valve, which are usually constructed from 3D CT images though many hours of manual annotation, and therefore an automatic valve shape reconstruction method is desired. In this paper, we present a method for estimating the aortic valve shape from 3D cardiac CT images, which is represented by triangle meshes. We propose a pipeline for aortic valve shape estimation which includes novel algorithms for building local shape dictionaries and for building landmark detectors and curve detectors using local shape dictionaries. The method is evaluated on real patient image dataset using a leave-one-out approach and achieves an average accuracy of 0.69 mm. The work will facilitate automatic patient-specific computational modeling of the aortic valve.

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

PubMed Central

Delbosc, Sandrine; Alsac, Jean-Marc; Journe, Clement; Louedec, Liliane; Castier, Yves; Bonnaure-Mallet, Martine; Ruimy, Raymond; Rossignol, Patrick; Bouchard, Philippe; Michel, Jean-Baptiste; Meilhac, Olivier

2011-01-01

Background Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. Methods and Findings Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. Conclusions Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. PMID:21533243

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

PubMed

Verbrugghe, Peter; Verhoeven, Jelle; Clijsters, Marnick; Vervoort, Dominique; Coudyzer, Walter; Verbeken, Eric; Meuris, Bart; Herijgers, Paul

2018-06-07

Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Side-Specific Endothelial-Dependent Regulation of Aortic Valve Calcification

PubMed Central

Richards, Jennifer; El-Hamamsy, Ismail; Chen, Si; Sarang, Zubair; Sarathchandra, Padmini; Yacoub, Magdi H.; Chester, Adrian H.; Butcher, Jonathan T.

2014-01-01

Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker l-NAME augmented calcification even in 3D VIC–VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and α-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology. PMID:23499458

Enhancing 4D PC-MRI in an aortic phantom considering numerical simulations

NASA Astrophysics Data System (ADS)

Kratzke, Jonas; Schoch, Nicolai; Weis, Christian; Müller-Eschner, Matthias; Speidel, Stefanie; Farag, Mina; Beller, Carsten J.; Heuveline, Vincent

2015-03-01

To date, cardiovascular surgery enables the treatment of a wide range of aortic pathologies. One of the current challenges in this field is given by the detection of high-risk patients for adverse aortic events, who should be treated electively. Reliable diagnostic parameters, which indicate the urge of treatment, have to be determined. Functional imaging by means of 4D phase contrast-magnetic resonance imaging (PC-MRI) enables the time-resolved measurement of blood flow velocity in 3D. Applied to aortic phantoms, three dimensional blood flow properties and their relation to adverse dynamics can be investigated in vitro. Emerging "in silico" methods of numerical simulation can supplement these measurements in computing additional information on crucial parameters. We propose a framework that complements 4D PC-MRI imaging by means of numerical simulation based on the Finite Element Method (FEM). The framework is developed on the basis of a prototypic aortic phantom and validated by 4D PC-MRI measurements of the phantom. Based on physical principles of biomechanics, the derived simulation depicts aortic blood flow properties and characteristics. The framework might help identifying factors that induce aortic pathologies such as aortic dilatation or aortic dissection. Alarming thresholds of parameters such as wall shear stress distribution can be evaluated. The combined techniques of 4D PC-MRI and numerical simulation can be used as complementary tools for risk-stratification of aortic pathology.

Aortic root segmentation in 4D transesophageal echocardiography

NASA Astrophysics Data System (ADS)

Chechani, Shubham; Suresh, Rahul; Patwardhan, Kedar A.

2018-02-01

The Aortic Valve (AV) is an important anatomical structure which lies on the left side of the human heart. The AV regulates the flow of oxygenated blood from the Left Ventricle (LV) to the rest of the body through aorta. Pathologies associated with the AV manifest themselves in structural and functional abnormalities of the valve. Clinical management of pathologies often requires repair, reconstruction or even replacement of the valve through surgical intervention. Assessment of these pathologies as well as determination of specific intervention procedure requires quantitative evaluation of the valvular anatomy. 4D (3D + t) Transesophageal Echocardiography (TEE) is a widely used imaging technique that clinicians use for quantitative assessment of cardiac structures. However, manual quantification of 3D structures is complex, time consuming and suffers from inter-observer variability. Towards this goal, we present a semiautomated approach for segmentation of the aortic root (AR) structure. Our approach requires user-initialized landmarks in two reference frames to provide AR segmentation for full cardiac cycle. We use `coarse-to-fine' B-spline Explicit Active Surface (BEAS) for AR segmentation and Masked Normalized Cross Correlation (NCC) method for AR tracking. Our method results in approximately 0.51 mm average localization error in comparison with ground truth annotation performed by clinical experts on 10 real patient cases (139 3D volumes).

Molecular and cellular mechanisms of aortic stenosis.

PubMed

Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls.

PubMed

Wang, S Keisin; Green, Linden A; Gutwein, Ashley R; Drucker, Natalie A; Motaganahalli, Raghu L; Gupta, Alok K; Fajardo, Andres; Murphy, Michael P

2018-04-28

The pathogenesis driving the formation of abdominal aortic aneurysms continues to be poorly understood. Therefore, we systemically define the cytokine and circulating immune cell environment observed in human abdominal aortic aneurysm compared with risk-factor matched controls. From 2015 to 2017, a total of 274 patients donated blood to the Indiana University Center for Aortic Disease. Absolute concentrations of circulating cytokines were determined, using enzyme-linked immunosorbent assays while the expression of circulating immune cell phenotypes were assayed via flow cytometric analysis. Human abdominal aortic aneurysm is characterized by a significant depletion of the antigen-specific, CD4 + Tr1 regulatory lymphocyte that corresponds to an upregulation of the antigen-specific, inflammatory Th17 cell. We found no differences in the incidence of Treg, B10, and myeloid-derived suppressor regulatory cells. Similarly, no disparities were noted in the following inflammatory cytokines: IL-1β, C-reactive protein, tumor necrosis factor α, interferon γ, and IL-23. However, significant upregulation of the inflammatory cytokines osteopontin, IL-6, and IL-17 were noted. Additionally, no changes were observed in the regulatory cytokines IL-2, IL-4, IL-13, TNF-stimulated gene 6 protein, and prostaglandin E2, but we did observe a significant decrease in the essential regulatory cytokine IL-10. In this investigation, we systematically characterize the abdominal aortic aneurysm-immune environment and present preliminary evidence that faulty immune regulation may also contribute to aneurysm formation and growth. Copyright © 2018 Elsevier Inc. All rights reserved.

Frozen Elephant Trunk and Antegrade Visceral Debranching in the Surgical Treatment of Type B Aortic Dissection: An Alternative Method

PubMed Central

Tuncer, Altug; Akbulut, Mustafa; Adademir, Taylan; Tas, Serpil; Ak, Adnan; Arslan, Özgür; Erden, Benay; Şişmanoğlu, Mesut

2016-01-01

Intervention is inevitable in complicated Type B aortic dissections. Classical surgical procedures and endovascular interventions are far from ideal treatments due to their high risk of periprocedural complications and mortality. There is often a need for alternative method in cases of difficult anatomy. We present the combined use of frozen elephant trunk and antegrade visceral debranching methods in the treatment of a 54-year-old male patient with complicated Type B aortic dissection. PMID:28516092

Oscillometric analysis compared with cardiac magnetic resonance for the assessment of aortic pulse wave velocity in patients with myocardial infarction.

PubMed

Feistritzer, Hans-Josef; Klug, Gert; Reinstadler, Sebastian J; Reindl, Martin; Mayr, Agnes; Schocke, Michael; Metzler, Bernhard

2016-09-01

Measurement of aortic pulse wave velocity (PWV) is the gold standard for assessment of aortic stiffness. In patients with ST-segment elevation myocardial infarction (STEMI), high aortic PWV has deleterious effects on the myocardium. In the present study, we compared a novel oscillometric device with cardiac magnetic resonance (CMR) imaging for the assessment of aortic PWV in STEMI patients. We measured aortic PWV in 60 reperfused STEMI patients using two different methods. The oscillometric method (PWVOSC) is based on mathematical transformation of brachial pressure waveforms, oscillometrically determined using a common cuff (Mobil-O-Graph, I.E.M., Stolberg, North Rhine-Westphalia, Germany). Phase-contrast CMR imaging (1.5 T scanner, Siemens, Erlangen, Bavaria, Germany) at the level of the ascending and abdominal aorta was performed to determine CMR-derived pulse wave velocity with the use of the transit time method. The mean age of the study population was 57 ± 11 years; 11 (18%) were women. Median PWVOSC was 7.4 m/s (interquartile range 6.8-8.9 m/s), and median CMR-derived pulse wave velocity was 6.3 m/s (interquartile range 5.7-8.2 m/s) (P < 0.001). A strong correlation was detected between both methods (r = 0.724, P < 0.001). Bland-Altman analysis revealed a bias of 0.62 m/s (upper and lower limit of agreement: 3.84 and -2.61 m/s). The coefficient of variation between both methods was 21%. In reperfused STEMI patients, aortic PWV assessed noninvasively by transformation of brachial pressure waveforms showed an acceptable agreement with the CMR-derived transit time method.

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

PubMed Central

Hamatani, Yasuhiro; Ishibashi-Ueda, Hatsue; Nagai, Toshiyuki; Sugano, Yasuo; Kanzaki, Hideaki; Yasuda, Satoshi; Fujita, Tomoyuki; Kobayashi, Junjiro; Anzai, Toshihisa

2016-01-01

Background Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated. Methods and Results We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients’ backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35). Conclusions Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV. PMID:27479126

Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

PubMed Central

Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

2015-01-01

Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

Spectrum of Aortic Valve Abnormalities Associated with Aortic Dilation Across Age Groups in Turner Syndrome

PubMed Central

Olivieri, Laura J.; Baba, Ridhwan Y.; Arai, Andrew E.; Bandettini, W. Patricia; Rosing, Douglas R.; Bakalov, Vladimir; Sachdev, Vandana; Bondy, Carolyn A.

2014-01-01

Background Congenital aortic valve fusion is associated with aortic dilation, aneurysm and rupture in girls and women with Turner syndrome (TS). Our objective was to characterize aortic valve structure in subjects with TS, and determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results The aortic valve and thoracic aorta were characterized by cardiovascular magnetic resonance imaging in 208 subjects with TS in an IRB-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve, and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve (TAV) 64%(n=133), partially fused aortic valve (PF) 12%(n=25), bicuspid aortic valve (BAV) 23%(n=47), and unicuspid aortic valve (UAV) 1%(n=3). Age and body surface area (BSA) were similar in the 4 valve morphology groups. There was a significant trend, independent of age, towards larger BSA-indexed ascending aortic diameters (AADi) with increasing valve fusion. AADi were (mean +/− SD) 16.9 +/− 3.3 mm/m2, 18.3 +/− 3.3 mm/m2, and 19.8 +/− 3.9 mm/m2 (p<0.0001) for TAV, PF and BAV+UAV respectively. PF, BAV, and UAV were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Conclusions Aortic valve abnormalities in TS occur with a spectrum of severity, and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased AADi. PMID:24084490

A new beating-heart mitral and aortic valve assessment model with implications for valve intervention training.

PubMed

Bouma, Wobbe; Jainandunsing, Jayant S; Khamooshian, Arash; van der Harst, Pim; Mariani, Massimo A; Natour, Ehsan

2017-02-01

A thorough understanding of mitral and aortic valve motion dynamics is essential in mastering the skills necessary for performing successful valve intervention (open or transcatheter repair or replacement). We describe a reproducible and versatile beating-heart mitral and aortic valve assessment and valve intervention training model in human cadavers. The model is constructed by bilateral ligation of the pulmonary veins, ligation of the supra-aortic arteries, creating a shunt between the descending thoracic aorta and the left atrial appendage with a vascular prosthesis, anastomizing a vascular prosthesis to the apex and positioning an intra-aortic balloon pump (IABP) in the vascular prosthesis, cross-clamping the descending thoracic aorta, and finally placing a fluid line in the shunt prosthesis. The left ventricle is filled with saline to the desired pressure through the fluid line, and the IABP is switched on and set to a desired frequency (usually 60-80 bpm). Prerepair valve dynamic motion can be studied under direct endoscopic visualization. After assessment, the IABP is switched off, and valve intervention training can be performed using standard techniques. This high-fidelity simulation model has known limitations, but provides a realistic environment with an actual beating (human) heart, which is of incremental value. The model provides a unique opportunity to fill a beating heart with saline and to study prerepair mitral and aortic valve dynamic motion under direct endoscopic visualization. The entire set-up provides a versatile beating-heart mitral and aortic valve assessment model, which may have important implications for future valve intervention training. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Comparison of aortic and carotid baroreflex stimulus-response characteristics in humans

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Weiss, M. W.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2001-01-01

In order to characterize the stimulus-response relationships of the arterial, aortic, and carotid baroreflexes in mediating cardiac chronotropic function, we measured heart rate (HR) responses elicited by acute changes in mean arterial pressure (MAP) and carotid sinus pressure (CSP) in 11 healthy individuals. Arterial (aortic + carotid) baroreflex control of HR was quantified using ramped changes in MAP induced by bolus injection of phenylephrine (PE) and sodium nitroprusside (SN). To assess aortic-cardiac responses, neck pressure (NP) and suction (NS) were applied during PE and SN administration, respectively, to counter alterations in CSP thereby isolating the aortic baroreflex. Graded levels of NP and NS were delivered to the carotid sinus using a customized neck collar device to assess the carotid-cardiac baroreflex, independent of drug infusion. The operating characteristics of each reflex were determined from the logistic function of the elicited HR response to the induced change in MAP. The arterial pressures at which the threshold was located on the stimulus-response curves determined for the arterial, aortic and carotid baroreflexes were not significantly different (72+/-4, 67+/-3, and 72+/-4 mm Hg, respectively, P > 0.05). Similarly, the MAP at which the saturation of the reflex responses were elicited did not differ among the baroreflex arcs examined (98+/-3, 99+/-2, and 102+/-3 mm Hg, respectively). These data suggest that the baroreceptor populations studied operate over the same range of arterial pressures. This finding indicates each baroreflex functions as both an important anti-hypotensive and anti-hypertensive mechanism. In addition, this investigation describes a model of aortic baroreflex function in normal healthy humans, which may prove useful in identifying the origin of baroreflex dysfunction in disease- and training-induced conditions.

[Use of an iliac branched endoprostheis in endovascular treatment for an abdominal aortic aneurysm combined with aneurysms of both common iliac arteries].

PubMed

Imaev, T E; Kuchin, I V; Lepilin, P M; Kolegaev, A S; Medvedeva, I S; Komlev, A E; Akchurin, R S

An abdominal aortic aneurysm appears to be combined with aneurysmatic lesions of the common iliac arteries in 30-40% of cases. Like abdominal aortic aneurysms, aneurysms of the common iliac arteries rarely manifest themselves clinically. The lethality rate in case of rupture is comparable to that for rupture of an abdominal aortic aneurysm. During endoprosthetic repair of abdominal aortic aneurysms combined with aneurysms of the common iliac arteries, in order to prevent endoleaks and to improve the distal zone of fixation of endografts surgeons often resort to embolization of internal iliac arteries, which may lead to ischaemic postoperative complications. One of the methods of preserving pelvic blood flow is the use of an iliac branched endograft. A series of studies evaluating long-term outcomes demonstrated that this method proved to be both safe and effective, and with the suitable anatomy is a method of choice in high surgical risk patients. The present article deals with a clinical case report concerning bilateral endoprosthetic repair of the common iliac arteries, combined with endoprosthetic repair of an abdominal aortic aneurysm, with the description of technical peculiarities of implanting an iliac branched graft.

Familial Thoracic Aortic Aneurysm with Dissection Presenting as Flash Pulmonary Edema in a 26-Year-Old Man

PubMed Central

Omar, Sabry; Moore, Tyler; Payne, Drew; Momeni, Parastoo; Mulkey, Zachary; Nugent, Kenneth

2014-01-01

We are reporting a case of familial thoracic aortic aneurysm and dissection in a 26-year-old man with no significant past medical history and a family history of dissecting aortic aneurysm in his mother at the age of 40. The patient presented with cough, shortness of breath, and chest pain. Chest X-ray showed bilateral pulmonary infiltrates. CT scan of the chest showed a dissection of the ascending aorta. The patient underwent aortic dissection repair and three months later he returned to our hospital with new complaints of back pain. CT angiography showed a new aortic dissection extending from the left carotid artery through the bifurcation and into the iliac arteries. The patient underwent replacement of the aortic root, ascending aorta, total aortic arch, and aortic valve. The patient recovered well postoperatively. Genetic studies of the patient and his children revealed no mutations in ACTA2, TGFBR1, TGFBR2, TGFB2, MYH11, MYLK, SMAD3, or FBN1. This case report focuses on a patient with familial TAAD and discusses the associated genetic loci and available screening methods. It is important to recognize potential cases of familial TAAD and understand the available screening methods since early diagnosis allows appropriate management of risk factors and treatment when necessary. PMID:25104961

Vascular tissue engineering by computer-aided laser micromachining.

PubMed

Doraiswamy, Anand; Narayan, Roger J

2010-04-28

Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

Cardiac Surgery in Patients Infected with Human Immunodeficiency Virus

PubMed Central

Abad, Cipriano; Cárdenes, Miguel Angel; Jiménez, Pedro Conrado; Armas, Mario-Vicente; Betancor, Pedro

2000-01-01

From January 1991 through December 1999, 5 consecutive patients who were infected with human immunodeficiency virus presented in need of cardiac surgery. All were men; the median age was 44 years. Two of them presented with mitral and aortic infectious valve endocarditis, 1 with tricuspid endocarditis, 1 with prosthetic valve endocarditis, and 1 with pericarditis and pericardial tamponade. Under cardiopulmonary bypass, the 4 patients with endocarditis underwent these procedures: mitral and aortic valve replacement (2), tricuspid valve replacement (1), and aortic valve replacement (reoperation) and concomitant repair of a mycotic ascending aortic aneurysm (1). In the patient who had pericardial effusion, subxifoid pericardiostomy and drainage were performed, and a pericardial window was created. There was no intraoperative mortality. The patient with pericardial effusion died 8 days after surgery; he was in septic shock and had multiple organ failure. Two deaths occurred at 2 and 63 months, due to hemoptysis and sudden death, respectively. The 2 patients who underwent double valve replacement are alive and in good condition after a median follow-up of 71 months. Cardiac surgery is indicated in selected patients infected by the human immunodeficiency virus. These patients are frequently drug abusers or homosexual. Valvular endocarditis is the most common finding. Hospital morbidity and mortality rates are higher than usual in this group of patients. PMID:11198308

Aortic operation after previous coronary artery bypass grafting: management of patent grafts for myocardial protection.

PubMed

Nakajima, Masato; Tsuchiya, Koji; Fukuda, Shoji; Morimoto, Hironobu; Mitsumori, Yoshitaka; Kato, Kaori

2006-04-01

Aortic surgery for progressive aortic valve disease or aortic aneurysm after previous coronary artery bypass grafting (CABG) is a challenging procedure. We report the outcome of aortic reoperation after previous CABG and evaluate our management of patent grafts and our methods for obtaining myocardial protection. From February 2001 to July 2003, 6 patients with progressive aortic valve disease and aneurysm of the thoracic aorta were operated on. The group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4 patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic dissection, and 1 with progressive aortic valve stenosis. The interval between previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were performed via median resternotomy. Myocardial protection was obtained by hypothermic perfusion of patent in-situ arterial grafts following cold-blood cardioplegia administration via the aortic root under aortic cross clamping. The operative procedure was aortic arch replacement in 4 patients, ascending aortic replacement with double CABG in 1, and aortic valve replacement in 1. All patients survived the reoperation. Postoperative maximum creatine kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram nor were any new wall motion abnormalities recognized on echocardiography. There were no late deaths during a follow-up of 30.7 months. Reoperative aortic procedures after CABG can be performed safely with myocardial protection via hypothermic perfusion of a patent in-situ arterial graft.

AT1-receptor blockade attenuates outward aortic remodeling associated with diet-induced obesity in mice.

PubMed

Krueger, Friedrich; Kappert, Kai; Foryst-Ludwig, Anna; Kramer, Frederike; Clemenz, Markus; Grzesiak, Aleksandra; Sommerfeld, Manuela; Paul Frese, Jan; Greiner, Andreas; Kintscher, Ulrich; Unger, Thomas; Kaschina, Elena

2017-08-01

The renin-angiotensin system (RAS) and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are not yet understood. We investigated the effect of the angiotensin receptor type 1 (AT1-receptor) antagonist telmisartan on aortic outward remodeling in a diet-induced obesity model in mice. C57/Black6J mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 14 weeks. One group of HFD mice was additionally exposed to telmisartan (3 mg/kg per day) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibers and decreased elastin content. Vascular damage was associated with up-regulation of matrix metalloproteinase (MMP)-2 (MMP-2), MMP-3, MMP-12, cathepsin D, and cathepsin B. HFD aortae exhibited an enhanced inflammatory status, characterized by tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) colocalized with adipocytes in the adventitia. HFD resulted in a significant increase in aortic dimensions, evident by ultrasound measurements. Telmisartan abolished aortic dilatation and preserved elastin content. HFD induced enhanced expression of aortic MMP-2, MMP-9, and TNF-α was abrogated by telmisartan. Adventitial proteolytic and inflammatory factors were also examined in samples from human abdominal aneurysms. The expression of TNF-α, IL-1β, and MMP-9 was higher in the adventitial fat of diseased vessels compared with healthy tissues. Finally, adipocytes treated with TNF-α showed enhanced MMP-2, MMP-3, and cathepsin D, which was prevented by telmisartan. Taken together, HFD in mice induced aortic dilatation with up-regulation of matrix degrading and inflammatory pathways similar to those seen in human aortic aneurysmatic tissue. The HFD-induced vascular pathology was reduced by AT1-receptor antagonist telmisartan. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Indication for percutaneous aortic valve implantation

PubMed Central

Akin, Ibrahim; Kische, Stephan; Rehders, Tim C.; Nienaber, Christoph A.; Rauchhaus, Mathias; Schneider, Henrik; Liebold, Andreas

2010-01-01

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively. PMID:22371763

Shape of the dilated aorta in children with bicuspid aortic valve

PubMed Central

Mart, Christopher R; McNerny, Bryn E

2013-01-01

Background: The dilated aorta in adults with bicuspid aortic valve has been shown to have different shapes, but it is not known if this occurs in children. This observational study was performed to determine if there are different shapes of the dilated aorta in children with bicuspid aortic valve and their association with age, gender, hemodynamic alterations, and degree of aortic enlargement. Methods: One hundred and eighty-seven echocardiograms done on pediatric patients (0 – 18 years) for bicuspid aortic valve, during 2008, were reviewed. Aortic valve morphology, shape/size of the aorta, and pertinent hemodynamic alterations were documented. Aortic dilation was felt to be present when at least one aortic segment had a z-score > 2.0; global aortic enlargement was determined by summing the aortic segment z-scores. The aortic shape was assessed by age, gender, valve morphology, and hemodynamic alterations. Results: Aortic dilation was present in 104/187 patients. The aorta had six different shapes designated from S1 through S6. There was no association between the aortic shape and gender, aortic valve morphology, or hemodynamic abnormalities. S3 was the most common after the age of six years and was associated with the most significant degree of global aortic enlargement. Conclusions: The shape of the dilated aorta in children with bicuspid aortic valve does not occur in a uniform manner and multiple shapes are seen. S2 and S3 are most commonly seen. As aortic dilation becomes more significant, a single shape (S3) becomes the dominant pattern. PMID:24688228

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Aortic Wave Dynamics and Its Influence on Left Ventricular Workload

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2010-11-01

Clinical and epidemiologic studies have shown that hypertension plays a key role in development of left ventricular (LV) hypertrophy and ultimately heart failure mostly due to increased LV workload. Therefore, it is crucial to diagnose and treat abnormal high LV workload at early stages. The pumping mechanism of the heart is pulsatile, thus it sends pressure and flow wave into the compliant aorta. The wave dynamics in the aorta is dominated by interplay of heart rate (HR), aortic rigidity, and location of reflection sites. We hypothesized that for a fixed cardiac output (CO) and peripheral resistance (PR), interplay of HR and aortic compliance can create conditions that minimize LV power requirement. We used a computational approach to test our hypothesis. Finite element method with direct coupling method of fluid-structure interaction (FSI) was used. Blood was assumed to be incompressible Newtonian fluid and aortic wall was considered elastic isotropic. Simulations were performed for various heart rates and aortic rigidities while inflow wave, CO, and PR were kept constant. For any aortic compliance, LV power requirement becomes minimal at a specific heart rate. The minimum shifts to higher heart rates as aortic rigidity increases.

Aortic Arch Aneurysms: Treatment with Extra anatomical Bypass and Endovascular Stent-Grafting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Noriyuki; Shimono, Takatsugu; Hirano, Tadanori

2002-10-15

Endovascular repair of thoracic aortic aneurysms is emerging as an attractive alternative to surgical graft replacement. However,patients with aortic arch aneurysms are often excluded from the target of endovascular repair because of lack of suitable landing zones, especially at the proximal ones. In this paper we describe our method for treating patients with aortic arch aneurysms using a combination of extra anatomical bypass surgery and endovascular stent-grafting.

Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

PubMed

Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

2018-06-01

Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive disease and small abdominal aortic aneurysm separately.

Ischemic Stroke in a Patient With Quadricuspid Aortic Valve and Patent Foramen Ovale

PubMed Central

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Moris, Demetrios; Tsiapras, Dimitrios; Voudris, Vassilis

2017-01-01

Quadricuspid aortic valve (QAV) is a rare congenital aortic valve abnormality. It is less common as compared to bicuspid or unicuspid aortic valve abnormality. QAV causes aortic regurgitation usually in the fifth to sixth decade of life. We present a rare case of a female patient with cryptogenic stroke due to a QAV and a patent foramen ovale (PFO). The patient underwent transcatheter closure of PFO, as there was no clear indication for surgery for her valve. Surgical removal remains the method of choice for the treatment of the QAV before left ventricular decompensation occurs. PMID:28868103

Ischemic Stroke in a Patient With Quadricuspid Aortic Valve and Patent Foramen Ovale.

PubMed

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Moris, Demetrios; Tsiapras, Dimitrios; Voudris, Vassilis

2017-08-01

Quadricuspid aortic valve (QAV) is a rare congenital aortic valve abnormality. It is less common as compared to bicuspid or unicuspid aortic valve abnormality. QAV causes aortic regurgitation usually in the fifth to sixth decade of life. We present a rare case of a female patient with cryptogenic stroke due to a QAV and a patent foramen ovale (PFO). The patient underwent transcatheter closure of PFO, as there was no clear indication for surgery for her valve. Surgical removal remains the method of choice for the treatment of the QAV before left ventricular decompensation occurs.

Immersed smoothed finite element method for fluid-structure interaction simulation of aortic valves

NASA Astrophysics Data System (ADS)

Yao, Jianyao; Liu, G. R.; Narmoneva, Daria A.; Hinton, Robert B.; Zhang, Zhi-Qian

2012-12-01

This paper presents a novel numerical method for simulating the fluid-structure interaction (FSI) problems when blood flows over aortic valves. The method uses the immersed boundary/element method and the smoothed finite element method and hence it is termed as IS-FEM. The IS-FEM is a partitioned approach and does not need a body-fitted mesh for FSI simulations. It consists of three main modules: the fluid solver, the solid solver and the FSI force solver. In this work, the blood is modeled as incompressible viscous flow and solved using the characteristic-based-split scheme with FEM for spacial discretization. The leaflets of the aortic valve are modeled as Mooney-Rivlin hyperelastic materials and solved using smoothed finite element method (or S-FEM). The FSI force is calculated on the Lagrangian fictitious fluid mesh that is identical to the moving solid mesh. The octree search and neighbor-to-neighbor schemes are used to detect efficiently the FSI pairs of fluid and solid cells. As an example, a 3D idealized model of aortic valve is modeled, and the opening process of the valve is simulated using the proposed IS-FEM. Numerical results indicate that the IS-FEM can serve as an efficient tool in the study of aortic valve dynamics to reveal the details of stresses in the aortic valves, the flow velocities in the blood, and the shear forces on the interfaces. This tool can also be applied to animal models studying disease processes and may ultimately translate to a new adaptive methods working with magnetic resonance images, leading to improvements on diagnostic and prognostic paradigms, as well as surgical planning, in the care of patients.

Relative biological effectiveness (RBE) of alpha radiation in cultured porcine aortic endothelial cells.

PubMed

Thomas, Patricia; Tracy, Bliss; Ping, Tilly; Baweja, Anar; Wickstrom, Mark; Sidhu, Narinder; Hiebert, Linda

2007-03-01

Northern peoples can receive elevated radiation doses (1- 10 mSv/y) from transfer of polonium-210 (210Po) through the lichen-caribou-human food chain. Ingested 210Po is primarily blood-borne and thus many of its short range alpha particles irradiate the endothelial cells lining the blood vessels. The relative biological effectiveness (RBE) of alpha particles vs. x-rays was examined in porcine aortic endothelial cells as a surrogate for understanding what might happen to human endothelial cells in northern populations consuming traditional foods. Cultured porcine aortic endothelial cells were exposed to x-ray and 210Po alpha particle radiation. Alpha irradiation was applied to the cell cultures internally via the culture medium and externally, using thin-bottomed culture dishes. The results given here are based on the external irradiation method, which was found to be more reliable. Dose-response curves were compared for four lethal endpoints (cell viability, live cell fraction, release of lactate dehydrogenase [LDH] and clonogenic survival) to determine the relative biological effectiveness (RBE) of alpha radiation. The alpha RBE for porcine cells varied from 1.6-21, depending on the endpoint: 21.2+/-4.5 for cell viability, 12.9+/-2.7 for decrease in live cell number, 5.3+/-0.4 for LDH release to the medium but only 1.6 +/-0.1 for clonogenic survival. The low RBE of 1.6 was due to x-ray hypersensitivity of endothelial cells at low doses.

Mechanics of cryopreserved aortic and pulmonary homografts.

PubMed

Vesely, I; Casarotto, D C; Gerosa, G

2000-01-01

The surgical placement of pulmonary valve grafts into the aortic position (the Ross procedure) has been performed for three decades. Cryopreserved pulmonary valves have had mixed clinical results, however. The objectives of this study were to compare the mechanics of cryopreserved human aortic and pulmonary valve cusps and roots to determine if the pulmonary root can withstand the greater pressures of the aortic position. Six aortic and six pulmonary valve roots were obtained from the Oxford Valve Bank. They were harvested during cardiac transplantation from hearts explanted for dilated cardiomyopathy (mean patient age 68 years). The whole roots were initially stored frozen at -186 degrees C, then shipped packed on dry ice. After complete thawing, the roots were pressurized whole; test strips were then cut from the valve cusps, roots and sinuses and tested for stress/strain, stress relaxation, and ultimate failure strength. The pulmonary roots were more distensible (30% versus 20% strain to lock-up) and less compliant when loaded to aortic pressures. The pulmonary valve cusp and root tissue also showed greater extensibility and greater stiffness (lower compliance) when subjected to the same loads. We conclude that mechanical differences between aortic and pulmonary valve tissues are minimal. The pulmonary root should withstand the forces imposed on it when placed in the aortic position. However, if implanted whole, the pulmonary root will distend about 30% more than the aortic root when subjected to aortic pressures. These geometric changes may affect valve function in the long term and should be appreciated when implanting a pulmonary valve graft.

Aortic root dynamics and surgery: from craft to science.

PubMed

Cheng, Allen; Dagum, Paul; Miller, D Craig

2007-08-29

Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure and functional dynamics of the aortic root throughout the cardiac cycle continues to elude investigators. The last five decades of experimental work have contributed substantially to our current understanding of aortic root dynamics. In this article, we review and summarize the relevant structural analyses, using radiopaque markers and sonomicrometric crystals, concerning aortic root three-dimensional deformations and describe aortic root dynamics in detail throughout the cardiac cycle. We then compare data between different studies and discuss the mechanisms responsible for the modes of aortic root deformation, including the haemodynamics, anatomical and temporal determinants of those deformations. These modes of aortic root deformation are closely coupled to maximize ejection, optimize transvalvular ejection haemodynamics and-perhaps most importantly-reduce stress on the aortic valve cusps by optimal diastolic load sharing and minimizing transvalvular turbulence throughout the cardiac cycle. This more comprehensive understanding of aortic root mechanics and physiology will contribute to improved medical and surgical treatment methods, enhanced therapeutic decision making and better post-intervention care of patients. With a better understanding of aortic root physiology, future research on aortic valve repair and replacement should take into account the integrated structural and functional asymmetry of aortic root dynamics to minimize stress on the aortic cusps in order to prevent premature structural valve deterioration.

Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis.

PubMed

Cochain, Clément; Vafadarnejad, Ehsan; Arampatzi, Panagiota; Jaroslav, Pelisek; Winkels, Holger; Ley, Klaus; Wolf, Dennis; Saliba, Antoine-Emmanuel; Zernecke, Alma

2018-03-15

Rationale: It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. Objective: We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. Methods and Results: We performed single-cell RNA sequencing of total aortic CD45 + cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr -/- mice. Unsupervised clustering singled out 13 distinct aortic cell clusters. Among the myeloid cell populations, Resident-like macrophages with a gene expression profile similar to aortic resident macrophages were found in healthy and diseased aortae, whereas monocytes, monocyte-derived dendritic cells (MoDC), and two populations of macrophages were almost exclusively detectable in atherosclerotic aortae, comprising Inflammatory macrophages showing enrichment in I l1b , and previously undescribed TREM2 hi macrophages. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these three macrophage subsets and MoDC, and uncovered putative functions of each cell type. Notably, TREM2 hi macrophages appeared to be endowed with specialized functions in lipid metabolism and catabolism, and presented a gene expression signature reminiscent of osteoclasts, suggesting a role in lesion calcification. TREM2 expression was moreover detected in human lesional macrophages. Importantly, these macrophage populations were present also in advanced atherosclerosis and in Apoe -/- aortae, indicating relevance of our findings in different stages of atherosclerosis and mouse models. Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic heterogeneity of aortic macrophages and MoDCs in atherosclerotic and identified previously unrecognized macrophage populations and their gene expression signature, suggesting specialized functions. Our findings will open up novel opportunities to explore distinct myeloid cell populations and their functions in atherosclerosis.

Aortic valve replacement using continuous suture technique in patients with aortic valve disease.

PubMed

Choi, Jong Bum; Kim, Jong Hun; Park, Hyun Kyu; Kim, Kyung Hwa; Kim, Min Ho; Kuh, Ja Hong; Jo, Jung Ku

2013-08-01

The continuous suture (CS) technique has several advantages as a method for simple, fast, and secure aortic valve replacement (AVR). We used a simple CS technique without the use of a pledget for AVR and evaluated the surgical outcomes. Between October 2007 and 2012, 123 patients with aortic valve disease underwent AVR alone (n=28) or with other concomitant cardiac procedures (n=95), such as mitral, tricuspid, or aortic surgery. The patients were divided into two groups: the interrupted suture (IS) group (n=47), in which the conventional IS technique was used, and the CS group (n=76), in which the simple CS technique was used. There were two hospital deaths (1.6%), which were not related to the suture technique. There were no significant differences in cardiopulmonary bypass time or aortic cross-clamp time between the two groups for AVR alone or AVR with concomitant cardiac procedures. In the IS group, two patients had prosthetic endocarditis and one patient experienced significant perivalvular leak. These patients underwent reoperations. In the CS group, there were no complications related to the surgery. Postoperatively, the two groups had similar aortic valve gradients. The simple CS method is useful and secure for AVR in patients with aortic valve disease, and it may minimize surgical complications, as neither pledgets nor braided sutures are used.

Calcific Aortic Valve Stenosis: Methods, Models, and Mechanisms

PubMed Central

Miller, Jordan D.; Weiss, Robert M.; Heistad, Donald D.

2011-01-01

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, non-osseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research. PMID:21617136

Label-free quantitative proteomic analysis of human plasma-derived microvesicles to find protein signatures of abdominal aortic aneurysms.

PubMed

Martinez-Pinna, Roxana; Gonzalez de Peredo, Anne; Monsarrat, Bernard; Burlet-Schiltz, Odile; Martin-Ventura, Jose Luis

2014-08-01

To find potential biomarkers of abdominal aortic aneurysms (AAA), we performed a differential proteomic study based on human plasma-derived microvesicles. Exosomes and microparticles isolated from plasma of AAA patients and control subjects (n = 10 each group) were analyzed by a label-free quantitative MS-based strategy. Homemade and publicly available software packages have been used for MS data analysis. The application of two kinds of bioinformatic tools allowed us to find differential protein profiles from AAA patients. Some of these proteins found by the two analysis methods belong to main pathological mechanisms of AAA such as oxidative stress, immune-inflammation, and thrombosis. Data analysis from label-free MS-based experiments requires the use of sophisticated bioinformatic approaches to perform quantitative studies from complex protein mixtures. The application of two of these bioinformatic tools provided us a preliminary list of differential proteins found in plasma-derived microvesicles not previously associated to AAA, which could help us to understand the pathological mechanisms related to this disease. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TGF-β mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease

PubMed Central

Munjal, Charu; Opoka, Amy M.; Osinska, Hanna; James, Jeanne F.; Bressan, Giorgio M.; Hinton, Robert B.

2014-01-01

Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1−/−) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1−/− aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1−/− aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD. PMID:25056700

Automatic aortic root segmentation in CTA whole-body dataset

NASA Astrophysics Data System (ADS)

Gao, Xinpei; Kitslaar, Pieter H.; Scholte, Arthur J. H. A.; Lelieveldt, Boudewijn P. F.; Dijkstra, Jouke; Reiber, Johan H. C.

2016-03-01

Trans-catheter aortic valve replacement (TAVR) is an evolving technique for patients with serious aortic stenosis disease. Typically, in this application a CTA data set is obtained of the patient's arterial system from the subclavian artery to the femoral arteries, to evaluate the quality of the vascular access route and analyze the aortic root to determine if and which prosthesis should be used. In this paper, we concentrate on the automated segmentation of the aortic root. The purpose of this study was to automatically segment the aortic root in computed tomography angiography (CTA) datasets to support TAVR procedures. The method in this study includes 4 major steps. First, the patient's cardiac CTA image was resampled to reduce the computation time. Next, the cardiac CTA image was segmented using an atlas-based approach. The most similar atlas was selected from a total of 8 atlases based on its image similarity to the input CTA image. Third, the aortic root segmentation from the previous step was transferred to the patient's whole-body CTA image by affine registration and refined in the fourth step using a deformable subdivision surface model fitting procedure based on image intensity. The pipeline was applied to 20 patients. The ground truth was created by an analyst who semi-automatically corrected the contours of the automatic method, where necessary. The average Dice similarity index between the segmentations of the automatic method and the ground truth was found to be 0.965±0.024. In conclusion, the current results are very promising.

Arterial waves in humans during peripheral vascular surgery.

PubMed

Khir, A W; Henein, M Y; Koh, T; Das, S K; Parker, K H; Gibson, D G

2001-12-01

The purpose of this study was to investigate the effect of aortic clamping on arterial waves during peripheral vascular surgery. We measured pressure and velocity simultaneously in the ascending aorta, in ten patients (70+/-5 years) with aortic-iliac disease intra-operatively. Pressure was measured using a catheter tip manometer, and velocity was measured using Doppler ultrasound. Data were collected before aortic clamping, during aortic clamping and after unclamping. Hydraulic work in the aortic root was calculated from the measured data, the reflected waves were determined by wave-intensity analysis and wave speed was determined by the PU-loop (pressure-velocity-loop) method; a new technique based on the 'water-hammer' equation. The wave speed is approx. 32% (P<0.05) higher during clamping than before clamping. Although the peak intensity of the reflected wave does not alter with clamping, it arrives 30 ms (P<0.05) earlier and its duration is 25% (P<0.05) longer than before clamping. During clamping, left ventricule (LV) hydraulic systolic work and the energy carried by the reflected wave increased by 27% (P<0.05) and 20% (P<0.05) respectively, compared with before clamping. The higher wave speed during clamping explains the earlier arrival of the reflected waves suggesting an increase in the afterload, since the LV has to overcome earlier reflected compression waves. The longer duration of the reflected wave during clamping is associated with an increase in the total energy carried by the wave, which causes an increase in hydraulic work. Increased hydraulic work during clamping may increase LV oxygen consumption, provoke myocardial ischaemia and hence contribute to the intra-operative impairment of LV function known in patients with peripheral vascular disease.

Segmentation of the Aortic Valve Apparatus in 3D Echocardiographic Images: Deformable Modeling of a Branching Medial Structure

PubMed Central

Pouch, Alison M.; Tian, Sijie; Takabe, Manabu; Wang, Hongzhi; Yuan, Jiefu; Cheung, Albert T.; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.; Yushkevich, Paul A.

2015-01-01

3D echocardiographic (3DE) imaging is a useful tool for assessing the complex geometry of the aortic valve apparatus. Segmentation of this structure in 3DE images is a challenging task that benefits from shape-guided deformable modeling methods, which enable inter-subject statistical shape comparison. Prior work demonstrates the efficacy of using continuous medial representation (cm-rep) as a shape descriptor for valve leaflets. However, its application to the entire aortic valve apparatus is limited since the structure has a branching medial geometry that cannot be explicitly parameterized in the original cm-rep framework. In this work, we show that the aortic valve apparatus can be accurately segmented using a new branching medial modeling paradigm. The segmentation method achieves a mean boundary displacement of 0.6 ± 0.1 mm (approximately one voxel) relative to manual segmentation on 11 3DE images of normal open aortic valves. This study demonstrates a promising approach for quantitative 3DE analysis of aortic valve morphology. PMID:26247062

Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

PubMed Central

Waters, Emily A; Chen, Junjie; Allen, John S; Zhang, Huiying; Lanza, Gregory M; Wickline, Samuel A

2008-01-01

Background Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of ανβ3 integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets. Methods New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with ανβ3 integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with ανβ3 integrin targeted PFC nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry. Results Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control animals. Nanoparticles were successfully detected in all samples scanned at 3.0T. PECAM endothelial staining and ανβ3 integrin staining revealed the presence of neovasculature within the valve leaflets. Conclusion Integrin-targeted PFC nanoparticles specifically detect early angiogenesis in sclerotic aortic valves of cholesterol fed rabbits. These techniques may be useful for assessing atherosclerotic components of preclinical aortic valve disease in patients and could assist in defining efficacy of medical therapies. PMID:18817557

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

USDA-ARS?s Scientific Manuscript database

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We ...

Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice.

PubMed

Tao, Ming; Yu, Peng; Nguyen, Binh T; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D; Virmani, Renu; Hao, Shuai; Ozaki, C Keith; Schneiderman, Jacob

2013-02-01

Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12. Leptin and leptin receptor antigen were evident in all AAAs, and leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched nondilated controls. To simulate in vivo local leptin synthesis, ApoE(-/-) mice were subjected to a paravisceral periaortic application of low-dose leptin. Leptin-treated aortas exhibited decreased transforming growth factor-β and increased MMP-9 mRNA levels 5 days after surgery, and leptin receptor mRNA was upregulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12, and periadventitial macrophage clustering. Furthermore, the combination of local periaortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Leptin is locally synthesized in human AAA wall. Paravisceral aortic leptin in ApoE(-/-) mice induces local medial degeneration and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation.

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

PubMed Central

Sierad, Leslie Neil; Shaw, Eliza Laine; Bina, Alexander; Brazile, Bryn; Rierson, Nicholas; Patnaik, Sourav S.; Kennamer, Allison; Odum, Rebekah; Cotoi, Ovidiu; Terezia, Preda; Branzaniuc, Klara; Smallwood, Harrison; Deac, Radu; Egyed, Imre; Pavai, Zoltan; Szanto, Annamaria; Harceaga, Lucian; Suciu, Horatiu; Raicea, Victor; Olah, Peter; Simionescu, Agneta; Liao, Jun; Movileanu, Ionela

2015-01-01

There is a great need for living valve replacements for patients of all ages. Such constructs could be built by tissue engineering, with perspective of the unique structure and biology of the aortic root. The aortic valve root is composed of several different tissues, and careful structural and functional consideration has to be given to each segment and component. Previous work has shown that immersion techniques are inadequate for whole-root decellularization, with the aortic wall segment being particularly resistant to decellularization. The aim of this study was to develop a differential pressure gradient perfusion system capable of being rigorous enough to decellularize the aortic root wall while gentle enough to preserve the integrity of the cusps. Fresh porcine aortic roots have been subjected to various regimens of perfusion decellularization using detergents and enzymes and results compared to immersion decellularized roots. Success criteria for evaluation of each root segment (cusp, muscle, sinus, wall) for decellularization completeness, tissue integrity, and valve functionality were defined using complementary methods of cell analysis (histology with nuclear and matrix stains and DNA analysis), biomechanics (biaxial and bending tests), and physiologic heart valve bioreactor testing (with advanced image analysis of open–close cycles and geometric orifice area measurement). Fully acellular porcine roots treated with the optimized method exhibited preserved macroscopic structures and microscopic matrix components, which translated into conserved anisotropic mechanical properties, including bending and excellent valve functionality when tested in aortic flow and pressure conditions. This study highlighted the importance of (1) adapting decellularization methods to specific target tissues, (2) combining several methods of cell analysis compared to relying solely on histology, (3) developing relevant valve-specific mechanical tests, and (4) in vitro testing of valve functionality. PMID:26467108

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection

PubMed Central

Cikach, Frank S.; Koch, Christopher D.; Mead, Timothy J.; Galatioto, Josephine; Willard, Belinda B.; Emerton, Kelly B.; Eagleton, Matthew J.; Blackstone, Eugene H.; Ramirez, Francesco; Roselli, Eric E.; Apte, Suneel S.

2018-01-01

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID:29515038

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

PubMed

Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

2018-03-08

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

PubMed

García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

2017-03-01

Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

Aortic assessment of bicuspid aortic valve patients and their first-degree relatives.

PubMed

Straneo, Pablo; Parma, Gabriel; Lluberas, Natalia; Marichal, Alvaro; Soca, Gerardo; Cura, Leandro; Paganini, Juan J; Brusich, Daniel; Florio, Lucia; Dayan, Victor

2017-03-01

Background Bicuspid aortic valve patients have an increased risk of aortic dilatation. A deficit of nitric oxide synthase has been proposed as the causative factor. No correlation between flow-mediated dilation and aortic diameter has been performed in patients with bicuspid aortic valves and normal aortic diameters. Being a hereditary disease, we compared echocardiographic features and endothelial function in these patients and their first-degree relatives. Methods Comprehensive physical examinations, routine laboratory tests, transthoracic echocardiography, and measurements of endothelium-dependent and non-dependent flow-mediated vasodilatation were performed in 18 bicuspid aortic valve patients (14 type 1 and 4 type 2) and 19 of their first-degree relatives. Results The first-degree relatives were younger (36.7 ± 18.8 vs. 50.5 ± 13.9 years, p = 0.019) with higher ejection fractions (64.6% ± 1.7% vs. 58.4% ± 9.5%, p = 0.015). Aortic diameters indexed to body surface area were similar in both groups, the except the tubular aorta which was larger in bicuspid aortic valve patients (19.3 ± 2.7 vs. 17.4 ± 2.2 mm·m -2 , p = 0.033). Flow-dependent vasodilation was similar in both groups. A significant inverse correlation was found between non-flow-dependent vasodilation and aortic root diameter in patients with bicuspid aortic valve ( R = -0.57, p = 0.05). Conclusions Bicuspid aortic valve patients without aortopathy have larger ascending aortic diameters than their first-degree relatives. Endothelial function is similar in both groups, and there is no correlation with ascending aorta diameter. Nonetheless, an inverse correlation exists between non-endothelial-dependent dilation and aortic root diameter in bicuspid aortic valve patients.

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino-acid-derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions and advanced atherosclerotic lesions.

PubMed Central

Hazen, S L; Gaut, J P; Crowley, J R; Hsu, F F; Heinecke, J W

2000-01-01

Reactive aldehydes might have a pivotal role in the pathogenesis of atherosclerosis by covalently modifying low-density lipoprotein (LDL). However, the identities of the aldehyde adducts that form on LDL in vivo are not yet clearly established. We previously demonstrated that the haem protein myeloperoxidase oxidizes proteins in the human artery wall. We also have shown that p-hydroxyphenylacetaldehyde (pHA), the aldehyde that forms when myeloperoxidase oxidizes L-tyrosine, covalently modifies the N(epsilon)-lysine residues of proteins. The resulting Schiff base can be quantified as N(epsilon)-[2-(p-hydroxyphenyl)ethyl]lysine (pHA-lysine) after reduction with NaCNBH(3). Here we demonstrate that pHA-lysine is a marker for LDL that has been modified by myeloperoxidase, and that water-soluble, but not lipid-soluble, antioxidants inhibit the modification of LDL protein. To determine whether myeloperoxidase-generated aldehydes might modify LDL in vivo, we used a combination of isotope-dilution GC-MS to quantify pHA-lysine in aortic tissues at various stages of lesion evolution. We also analysed LDL isolated from atherosclerotic aortic tissue. Comparison of normal and atherosclerotic aortic tissue demonstrated a significant elevation (more than 10-fold) of the reduced Schiff base adduct in fatty streaks, intermediate lesions and advanced lesions compared with normal aortic tissue. Moreover, the level of pHA-lysine in LDL recovered from atherosclerotic aortic intima was 200-fold that in plasma LDL of healthy donors. These results indicate that pHA-lysine, a specific covalent modification of LDL, is generated in human atherosclerotic vascular tissue. They also raise the possibility that reactive aldehydes generated by myeloperoxidase have a role in converting LDL into an atherogenic lipoprotein. PMID:11104675

Four Surgical Modifications to the Classic Elastase Perfusion Aneurysm Model Enable Haemodynamic Alterations and Extended Elastase Perfusion.

PubMed

Busch, Albert; Chernogubova, Ekaterina; Jin, Hong; Meurer, Felix; Eckstein, Hans-Henning; Kim, Mia; Maegdefessel, Lars

2018-04-24

Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in today's ageing society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair. For research purposes, animal models are necessary and the elastase induced aneurysm model closely mimics end stage human aneurysm disease. To improve the translational value of this model, four modifications to the classic elastase perfusion procedure (PPE) in relation to human aneurysm morphology were conducted. In ten week old male C57BL/6J wild type mice the PPE procedure was modified in four ways using two different techniques. Flow alteration was simulated by partial ligation of the common iliac artery or the distal aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound, and immunohistochemistry were used to evaluate these pilot results. Two aortic outflow obstructions simulating distal aortic or iliac stenosis significantly increase murine AAA diameter (p = .046), and affect local vascular wall remodelling. Suprarenal aortic dissection allows a juxtarenal aneurysm to be induced, similar to the angiotensin II induced aneurysm model. A separate investigation for canonical activation of transforming growth factor β in the two embryonically distinct juxtarenal and infrarenal segments showed no distinct difference. Creating an aortoiliac bifurcated aneurysm completes the mimicry of human aneurysm morphology. The alteration of the classic PPE aneurysm by outflow modulation and further elastase perfusion to the juxtarenal and aortoiliac segment modifies morphology and diameter, and thus increases the translational value in future research. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

[Non-invasive estimation of aortic flow by local electrical impedance changes].

PubMed

Okuda, N; Ohashi, N; Yamada, M; Fujinami, T

1986-09-01

Aortic flow velocity was measured by catheter-tip flow transducer in 25 patients who underwent left cardiac catheterization for non-invasive estimates by the impedance method. Disk electrodes were attached to the skin at the levels of the second thoracic vertebra in the posterior median line and the V8 lead position for electrocardiography. Alternating current, 350 micro-amperes, 50 KHz constant, was applied to the outer electrode, and impedance changes were detected via the inner electrode. The e wave, or height of the first derivative dz/dt wave of the electrical impedance was lower in cases of old myocardial infarction and higher in cases of aortic valve regurgitation, as compared with the values of the healthy control group. The time lag between the start of the upward deflection and the peak value of the dz/dt wave coincided with that of the aortic flow curve as measured at the aortic arch and descending aorta. These time lags were about 20 to 30 msec as compared with the ascending aortic flow curve, and were -20 to -30 msec as compared with the abdominal aortic flow curve. There was a close correlation between the maximum flow velocity measured at the aortic arch and the height of the e waves. The regression equation was: Y = 0.21X - 1.53, r = 0.88, p less than 0.01. These data suggest that the first derivative of electrical impedance change as obtained by the disk electrode method reflects aortic flow at the arch and descending aorta.

Time to aortic occlusion: It's all about access.

PubMed

Romagnoli, Anna; Teeter, William; Pasley, Jason; Hu, Peter; Hoehn, Melanie; Stein, Deborah; Scalea, Thomas; Brenner, Megan

2017-12-01

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less invasive method of proximal aortic occlusion compared with resuscitative thoracotomy with aortic cross-clamping (RTACC). This study compared time to aortic occlusion with REBOA and RTACC, both including and excluding time required for common femoral artery (CFA) cannulation. This was a retrospective, single-institution review of REBOA or RTACC performed between February 2013 and January 2016. Time of skin incision to aortic cross-clamp for RTACC, time required for CFA cannulation by percutaneous and open methods, and time from guide-wire insertion to balloon inflation at Zone 1 for REBOA, were obtained from videographic recordings. Eighteen RTACC and 21 REBOAs were performed. Median (Q1, Q3) time from skin incision to aortic cross-clamping was 317 seconds (227, 551 seconds). Median (Q1, Q3) time from start of arterial access to Zone 1 balloon occlusion was 474 seconds (431, 572 seconds) (vs. RTACC, p = 0.01). All REBOA procedures were performed with the same device. The median time to complete CFA cannulation was 247 seconds (range, 164-343 seconds), with no difference between percutaneous or open procedures (p = 0.07). The median (Q1, Q3) time to aortic occlusion in REBOA once arterial access had been established was 245 seconds (179, 295.5 seconds), which was significantly shorter than RTACC (p = 0.003). Once CFA access is achieved, time to aortic occlusion is faster with REBOA. Time to aortic occlusion is less than the time required to cannulate the CFA either by percutaneous or open approaches, emphasizing the importance of accurate and expedient CFA access. Resuscitative endovascular balloon occlusion of the aorta may represent a feasible alternative to thoracotomy for aortic occlusion. Time to aortic occlusion will likely decrease with the advent of newer REBOA technology. The rate-limiting portion of REBOA continues to be obtaining CFA access. Therapeutic, level V.

Shape-based diagnosis of the aortic valve

NASA Astrophysics Data System (ADS)

Ionasec, Razvan Ioan; Tsymbal, Alexey; Vitanovski, Dime; Georgescu, Bogdan; Zhou, S. Kevin; Navab, Nassir; Comaniciu, Dorin

2009-02-01

Disorders of the aortic valve represent a common cardiovascular disease and an important public-health problem worldwide. Pathological valves are currently determined from 2D images through elaborate qualitative evalu- ations and complex measurements, potentially inaccurate and tedious to acquire. This paper presents a novel diagnostic method, which identies diseased valves based on 3D geometrical models constructed from volumetric data. A parametric model, which includes relevant anatomic landmarks as well as the aortic root and lea ets, represents the morphology of the aortic valve. Recently developed robust segmentation methods are applied to estimate the patient specic model parameters from end-diastolic cardiac CT volumes. A discriminative distance function, learned from equivalence constraints in the product space of shape coordinates, determines the corresponding pathology class based on the shape information encoded by the model. Experiments on a heterogeneous set of 63 patients aected by various diseases demonstrated the performance of our method with 94% correctly classied valves.

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

PubMed Central

Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

2015-01-01

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. PMID:26308526

Investigation of pulsatile flowfield in healthy thoracic aorta models.

PubMed

Wen, Chih-Yung; Yang, An-Shik; Tseng, Li-Yu; Chai, Jyh-Wen

2010-02-01

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics plays a critical role in the development of aortic dissection and atherosclerosis, as well as many other diseases. Since fundamental fluid mechanics are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects, a joint experimental and numerical study was conducted in this study to determine the distributions of wall shear stress and pressure and oscillatory WSS index, and to examine their correlation with the aortic disorders, especially dissection. Experimentally, the Phase-Contrast Magnetic Resonance Imaging (PC-MRI) method was used to acquire the true geometry of a normal human thoracic aorta, which was readily converted into a transparent thoracic aorta model by the rapid prototyping (RP) technique. The thoracic aorta model was then used in the in vitro experiments and computations. Simulations were performed using the computational fluid dynamic (CFD) code ACE+((R)) to determine flow characteristics of the three-dimensional, pulsatile, incompressible, and Newtonian fluid in the thoracic aorta model. The unsteady boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured flowrate and pressure results during in vitro experiments. For the code validation, the predicted axial velocity reasonably agrees with the PC-MRI experimental data in the oblique sagittal plane of the thoracic aorta model. The thorough analyses of the thoracic aorta flow, WSSs, WSS index (OSI), and wall pressures are presented. The predicted locations of the maxima of WSS and the wall pressure can be then correlated with that of the thoracic aorta dissection, and thereby may lead to a useful biological significance. The numerical results also suggest that the effects of low WSS and high OSI tend to cause wall thickening occurred along the inferior wall of the aortic arch and the anterior wall of the brachiocephalic artery, similar implication reported in a number of previous studies.

H19 Induces Abdominal Aortic Aneurysm Development and Progression.

PubMed

Li, Daniel Y; Busch, Albert; Jin, Hong; Chernogubova, Ekaterina; Pelisek, Jaroslav; Karlsson, Joakim; Sennblad, Bengt; Liu, Shengliang; Lao, Shen; Hofmann, Patrick; Bäcklund, Alexandra; Eken, Suzanne M; Roy, Joy; Eriksson, Per; Dacken, Brian; Ramanujam, Deepak; Dueck, Anne; Engelhardt, Stefan; Boon, Reinier A; Eckstein, Hans-Henning; Spin, Joshua M; Tsao, Philip S; Maegdefessel, Lars

2018-04-18

Background -Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize lncRNAs as potential mediators in abdominal aortic aneurysm (AAA) development. Methods -We profiled RNA transcript expression in two murine AAA models, Angiotensin II (ANGII) infusion in ApoE-/- mice ( n =8) and porcine pancreatic elastase (PPE) instillation in C57BL/6 wildtype mice ( n =12). The lncRNA H19 was identified as one of the most highly up-regulated transcripts in both mouse aneurysm models compared to sham-operated controls. This was confirmed by qRT-PCR and in situ hybridization. Results -Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo , significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human AAA tissue samples, and in a novel preclinical LDLR-/- Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, while overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1-alpha (HIF1α) as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and HIF1α and sequential p53 stabilization. Additionally, H19 induced transcription of HIF1α via recruiting the transcription factor specificity protein 1 (Sp1) to the promoter region. Conclusions -The lncRNA H19 is a novel regulator of SMC survival in AAA development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

PubMed

Braun, Fabian; Proença, Martin; Rapin, Michael; Lemay, Mathieu; Adler, Andy; Grychtol, Bartłomiej; Solà, Josep; Thiran, Jean-Philippe

2015-06-01

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT). However, finding the aortic signal within EIT image sequences is a challenging task: the signal has a small amplitude and is difficult to locate due to the small size of the aorta and the inherent low spatial resolution of EIT. In order to most reliably detect the aortic signal, our objective was to understand the effect of EIT measurement settings (electrode belt placement, reconstruction algorithm). This paper investigates the influence of three transversal belt placements and two commonly-used difference reconstruction algorithms (Gauss-Newton and GREIT) on the measurement of aortic signals in view of aortic blood pressure estimation via EIT. A magnetic resonance imaging based three-dimensional finite element model of the haemodynamic bio-impedance properties of the human thorax was created. Two simulation experiments were performed with the aim to (1) evaluate the timing error in aortic PAT estimation and (2) quantify the strength of the aortic signal in each pixel of the EIT image sequences. Both experiments reveal better performance for images reconstructed with Gauss-Newton (with a noise figure of 0.5 or above) and a belt placement at the height of the heart or higher. According to the noise-free scenarios simulated, the uncertainty in the analysis of the aortic EIT signal is expected to induce blood pressure errors of at least ± 1.4 mmHg.

Treatment of aortic stenosis with aortic valve bypass (apicoaortic conduit) surgery: an assessment using computational modeling.

PubMed

Balaras, Elias; Cha, K S; Griffith, Bartley P; Gammie, James S

2009-03-01

Aortic valve bypass surgery treats aortic valve stenosis with a valve-containing conduit that connects the left ventricular apex to the descending thoracic aorta. After aortic valve bypass, blood is ejected from the left ventricle via both the native stenotic aortic valve and the conduit. We performed computational modeling to determine the effects of aortic valve bypass on aortic and cerebral blood flow, as well as the effect of conduit size on relative blood flow through the conduit and the native valve. The interaction of blood flow with the vascular boundary was modeled using a hybrid Eurelian-Lagrangian formulation, where an unstructured Galerkin finite element method was coupled with an immersed boundary approach. Our model predicted native (stenotic) valve to conduit flow ratios of 45:55, 52:48, and 60:40 for conduits with diameters of 20, 16, and 10 mm, respectively. Mean gradients across the native aortic valve were calculated to be 12.5, 13.8, and 17.6 mm Hg, respectively. Post-aortic valve bypass cerebral blood flow was unchanged from preoperative aortic valve stenosis configurations and was constant across all conduit sizes. In all cases modeled, cerebral blood flow was completely supplied by blood ejected across the native aortic valve. An aortic valve bypass conduit as small as 10 mm results in excellent relief of left ventricular outflow tract obstruction in critical aortic valve stenosis. The presence of an aortic valve bypass conduit has no effect on cerebral blood flow. All blood flow to the brain occurs via antegrade flow across the native stenotic valve; this configuration may decrease the long-term risk of cerebral thromboembolism.

Aortic stiffness and calcification in men in a population-based international study

PubMed Central

Sekikawa, Akira; Shin, Chol; Curb, J. David; Barinas-Mitchell, Emma; Masaki, Kamal; El-Saed, Aiman; Seto, Todd B.; Mackey, Rachel H.; Choo, Jina; Fujiyoshi, Akira; Miura, Katsuyuki; Edmundowicz, Daniel; Kuller, Lewis H.; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim

2012-01-01

Objectives Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. Methods We examined the association in 906 men aged 40–49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. Results Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1–100 (n=411), 101–300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. Conclusions The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40’s. PMID:22537531

Fatal Saccharomyces Cerevisiae Aortic Graft Infection

NASA Technical Reports Server (NTRS)

Meyer, Michael (Technical Monitor); Smith, Davey; Metzgar, David; Wills, Christopher; Fierer, Joshua

2002-01-01

Saccharomyces cerevisiae is a yeast commonly used in baking and a frequent colonizer of human mucosal surfaces. It is considered relatively nonpathogenic in immunocompetent adults. We present a case of S. cerevisiae fungemia and aortic graft infection in an immunocompetent adult. This is the first reported case of S. cerevisiue fungemia where the identity of the pathogen was confirmed by rRNA sequencing.

Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and Abdominal Aortic Aneurysms

PubMed Central

Venkatesh, Premakumari; Phillippi, Julie; Chukkapalli, Sasanka; Rivera-Kweh, Mercedes; Velsko, Irina; Gleason, Thomas; VanRyzin, Paul; Aalaei-Andabili, Seyed Hossein; Ghanta, Ravi Kiran; Beaver, Thomas; Chan, Edward Kar Leung; Kesavalu, Lakshmyya

2017-01-01

Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486-5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm location and common to both thoracic and abdominal pathologies. Thus, changes in miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p impact AAAs. This work validates prior studies on microRNA expression in aneurysmal diseases. PMID:28425970

Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and Abdominal Aortic Aneurysms.

PubMed

Venkatesh, Premakumari; Phillippi, Julie; Chukkapalli, Sasanka; Rivera-Kweh, Mercedes; Velsko, Irina; Gleason, Thomas; VanRyzin, Paul; Aalaei-Andabili, Seyed Hossein; Ghanta, Ravi Kiran; Beaver, Thomas; Chan, Edward Kar Leung; Kesavalu, Lakshmyya

2017-04-20

Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486-5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm location and common to both thoracic and abdominal pathologies. Thus, changes in miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p impact AAAs. This work validates prior studies on microRNA expression in aneurysmal diseases.

Redox stress in Marfan syndrome: Dissecting the role of the NADPH oxidase NOX4 in aortic aneurysm.

PubMed

Jiménez-Altayó, Francesc; Meirelles, Thayna; Crosas-Molist, Eva; Sorolla, M Alba; Del Blanco, Darya Gorbenko; López-Luque, Judit; Mas-Stachurska, Aleksandra; Siegert, Ana-Maria; Bonorino, Fabio; Barberà, Laura; García, Carolina; Condom, Enric; Sitges, Marta; Rodríguez-Pascual, Fernando; Laurindo, Francisco; Schröder, Katrin; Ros, Joaquim; Fabregat, Isabel; Egea, Gustavo

2018-04-01

Marfan syndrome (MFS) is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix fibrillin-containing microfibrils and dysfunction of TGF-β signaling. Here we identify the molecular targets of redox stress in aortic aneurysms from MFS patients, and investigate the role of NOX4, whose expression is strongly induced by TGF-β, in aneurysm formation and progression in a murine model of MFS. Working models included aortae and cultured vascular smooth muscle cells (VSMC) from MFS patients, and a NOX4-deficient Marfan mouse model (Fbn1 C1039G/+ -Nox4 -/- ). Increased tyrosine nitration and reactive oxygen species levels were found in the tunica media of human aortic aneurysms and in cultured VSMC. Proteomic analysis identified nitrated and carbonylated proteins, which included smooth muscle α-actin (αSMA) and annexin A2. NOX4 immunostaining increased in the tunica media of human Marfan aorta and was transcriptionally overexpressed in VSMC. Fbn1 C1039G/+ -Nox4 -/- mice aortas showed a reduction of fragmented elastic fibers, which was accompanied by an amelioration in the Marfan-associated enlargement of the aortic root. Increase in the contractile phenotype marker calponin in the tunica media of MFS mice aortas was abrogated in Fbn1 C1039G/+ -Nox4 -/- mice. Endothelial dysfunction evaluated by myography in the Marfan ascending aorta was prevented by the absence of Nox4 or catalase-induced H 2 O 2 decomposition. We conclude that redox stress occurs in MFS, whose targets are actin-based cytoskeleton members and regulators of extracellular matrix homeostasis. Likewise, NOX4 have an impact in the progression of the aortic dilation in MFS and in the structural organization of the aortic tunica media, the VSMC phenotypic modulation, and endothelial function. Copyright © 2018 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagy, Edit, E-mail: edit.nagy@karolinska.se; Department of Cardiology, Karolinska University Hospital, Stockholm; Caidahl, Kenneth

Highlights: Black-Right-Pointing-Pointer Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. Black-Right-Pointing-Pointer We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. Black-Right-Pointing-Pointer Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. Black-Right-Pointing-Pointer The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. Black-Right-Pointing-Pointer Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis,more » and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C{sub 4} (LTC{sub 4}) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = -0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = -0.498; P = 0.0298) only in tricuspid aortic valves. LTC{sub 4} (1 nM) significantly elevated the mRNA levels of PARP-1 by 2.38-fold in VICs. Taken together, these data suggest that valvular DNA-damage pathways may be associated with inflammation and the stenosis severity in tricuspid aortic valves.« less

Human aortic endothelial cell morphology influenced by topography of porous silicon substrates.

PubMed

Formentín, Pilar; Catalán, Úrsula; Fernández-Castillejo, Sara; Alba, Maria; Baranowska, Malgorzata; Solà, Rosa; Pallarès, Josep; Marsal, Lluís F

2015-10-01

Porous silicon has received much attention because of its optical properties and for its usefulness in cell-based biosensing, drug delivery, and tissue engineering applications. Surface properties of the biomaterial are associated with cell adhesion and with proliferation, migration, and differentiation. The present article analyzes the behavior of human aortic endothelial cells in macro- and nanoporous collagen-modified porous silicon samples. On both substrates, cells are well adhered and numerous. Confocal microscopy and scanning electron microscopy were employed to study the effects of porosity on the morphology of the cells. On macroporous silicon, filopodia is not observed but the cell spreads on the surface, increasing the lamellipodia surface which penetrates the macropore. On nanoporous silicon, multiple filopodia were found to branch out from the cell body. These results demonstrate that the pore size plays a key role in controlling the morphology and growth rate of human aortic endothelial cells, and that these forms of silicon can be used to control cell development in tissue engineering as well as in basic cell biology research. © The Author(s) 2015.

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

PubMed

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

2017-11-15

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Suspension string: a new method of aortic valvuloplasty for aortic insufficiency and ventricular septal defect.

PubMed

Huang, Zhixiong

2006-09-01

In a 4-year-old boy with ventricular septal defect, severe aortic insufficiency, and mild infundibular stenosis, a new method was used to reconstruct the prolapsed aortic cusp. Two ends of a pledged stitch were passed through the aorta at each side of the right, noncoronary commissure and then through another pledget, and were then tied repeatedly in a row. The length of the row of knots was equal to that of the free edge of left coronary or noncoronary leaflet. The remainder of the stitch was passed through a pledget and then the aortic wall at each side of the left and right coronary commissure to the extraaortic wall pledget and were tied. A suspension string was formed by the row of knots and supported by a Teflon (Dupont Teflon, Wilmington, DE) felt pledget sandwich at each of two commissures. The free margin of the prolapsed cusp was attached to the suspension string by a continuous suture. The concomitant anomalies were corrected. The result was satisfactory.

Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

PubMed

Kamoi, S; Pretty, C G; Chiew, Y S; Pironet, A; Davidson, S; Desaive, T; Shaw, G M; Chase, J G

2015-08-01

Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

Dilatation of the initially non-aneurysmal ascending aorta after replacement of a bicuspid versus tricuspid aortic valve.

PubMed

Zhang, Jing; Fan, Guangpu; Zhao, Hui; Wang, Xu; Wang, Zhiwei; Zhang, Peide; Wang, Wei

2016-12-01

Objective To compare the aortic diameter after isolated aortic valve replacement (AVR) in patients with a bicuspid (BAV) or tricuspid aortic valve (TAV) and an initially normal ascending aorta. Methods Patients with an ascending aortic diameter of < 45 mm who had undergone isolated AVR were studied. Ultrasonic cardiographic measurements of the ascending aortic diameter made pre- and postoperatively and follow-up data concerning adverse aortic events and death were analyzed. Results A total of 613 patients were included in this retrospective study; of these, 211 had a BAV and 402 had a TAV. In both groups, the ascending aorta significantly expanded but was non-aneurysmal during follow-up; however, the difference between the two groups was not significant. Cox regression analysis showed no significant effect associated with the presence of a BAV on adverse aortic events or death. Conclusion Dilatation of the ascending aorta was observed after AVR in both groups, but was not more pronounced in patients with a BAV. Long-term follow-up for ascending aortic aneurysm is necessary after AVR in both patients with a BAV and those with a TAV.

Dilatation of the initially non-aneurysmal ascending aorta after replacement of a bicuspid versus tricuspid aortic valve

PubMed Central

Zhang, Jing; Fan, Guangpu; Zhao, Hui; Wang, Xu; Wang, Zhiwei; Zhang, Peide

2016-01-01

Objective To compare the aortic diameter after isolated aortic valve replacement (AVR) in patients with a bicuspid (BAV) or tricuspid aortic valve (TAV) and an initially normal ascending aorta. Methods Patients with an ascending aortic diameter of < 45 mm who had undergone isolated AVR were studied. Ultrasonic cardiographic measurements of the ascending aortic diameter made pre- and postoperatively and follow-up data concerning adverse aortic events and death were analyzed. Results A total of 613 patients were included in this retrospective study; of these, 211 had a BAV and 402 had a TAV. In both groups, the ascending aorta significantly expanded but was non-aneurysmal during follow-up; however, the difference between the two groups was not significant. Cox regression analysis showed no significant effect associated with the presence of a BAV on adverse aortic events or death. Conclusion Dilatation of the ascending aorta was observed after AVR in both groups, but was not more pronounced in patients with a BAV. Long-term follow-up for ascending aortic aneurysm is necessary after AVR in both patients with a BAV and those with a TAV. PMID:27484890

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

PubMed

Backer, Julie De; Braverman, Alan C

2018-05-01

Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Phasic changes in human right coronary blood flow before and after repair of aortic insufficiency.

PubMed

Folts, J D; Rowe, G G; Kahn, D R; Young, W P

1979-02-01

We have shown previously that acute aortic insufficiency in chronically instrumented dogs reverses the normally high ratio of diastolic to systolic coronary blood flow. Phasic blood flow in the dominant right coronary artery was measured directly with an electromagnetic flow meter during surgery in eight patients with severe aortic insufficiency before and after relacement of the aortic valve. Before the insufficiency was eliminated, right coronary flow average 116 +/- 37 ml./minute and the diastolic to systolic flow ratio was 0.88 +/- 17. Mean arterial blood pressure averaged 106 +/- 17 mm. Hg, heart rate 84 +/- 19 beats/minute, and mean diastolic pressure averaged 67 +/- 10 mm. Hg. After the aortic valve was replaced with an average heart rate of 90 +/- 15 and mean blood pressure of 103 +/- 13 mm. Hg, the average right coronary blood flow increased to 180 +/- 40 ml./minute with a D/S ratio of 2.18 +/- 0.8. In all cases the right coronary blood flow increased after the aortic insufficiency was eliminated surgically. Right coronary flow probably increased because of the improved diastolic perfusion pressure and the change from predominantly systolic to diastolic coronary flow.

Comparison of an oscillometric method with cardiac magnetic resonance for the analysis of aortic pulse wave velocity.

PubMed

Feistritzer, Hans-Josef; Reinstadler, Sebastian J; Klug, Gert; Kremser, Christian; Seidner, Benjamin; Esterhammer, Regina; Schocke, Michael F; Franz, Wolfgang-Michael; Metzler, Bernhard

2015-01-01

Pulse wave velocity (PWV) is the proposed gold-standard for the assessment of aortic elastic properties. The aim of this study was to compare aortic PWV determined by a recently developed oscillometric device with cardiac magnetic resonance imaging (CMR). PWV was assessed in 40 volunteers with two different methods. The oscillometric method (PWVOSC) is based on a transfer function from the brachial pressure waves determined by oscillometric blood pressure measurements with a common cuff (Mobil-O-Graph, I.E.M. Stolberg, Germany). CMR was used to determine aortic PWVCMR with the use of the transit time method based on phase-contrast imaging at the level of the ascending and abdominal aorta on a clinical 1.5 Tesla scanner (Siemens, Erlangen, Germany). The median age of the study population was 34 years (IQR: 24-55 years, 11 females). A very strong correlation was found between PWVOSC and PWVCMR (r = 0.859, p < 0.001). Mean PWVOSC was 6.7 ± 1.8 m/s and mean PWVCMR was 6.1 ± 1.8 m/s (p < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 0.57 m/s (upper and lower limit of agreement: 2.49 m/s and -1.34 m/s). The corresponding coefficient of variation between both measurements was 15%. Aortic pulse wave velocity assessed by transformation of the brachial pressure waveform showed an acceptable agreement with the CMR-derived transit time method.

Medical Treatment of Aortic Aneurysms in Marfan Syndrome and other Heritable Conditions

PubMed Central

Jost, Christine H. Attenhofer; Greutmann, Matthias; Connolly, Heidi M.; Weber, Roland; Rohrbach, Marianne; Oxenius, Angela; Kretschmar, Oliver; Luscher, Thomas F.; Matyas, Gabor

2014-01-01

Thoracic aortic aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS) and related aortic diseases as well as by inflammatory disorders such as giant cell arteritis or atherosclerosis. In all these conditions, cardiovascular risk factors, such as systemic arterial hypertension, may contribute to faster rate of aneurysm progression. Optimal medical management to prevent progressive aortic dilatation and aortic dissection is unknown. β-blockers have been the mainstay of medical treatment for many years despite limited evidence of beneficial effects. Recently, losartan, an angiotensin II type I receptor antagonist (ARB), has shown promising results in a mouse model of MFS and subsequently in humans with MFS and hence is increasingly used. Several ongoing trials comparing losartan to β-blockers and/or placebo will better define the role of ARBs in the near future. In addition, other medications, such as statins and tetracyclines have demonstrated potential benefit in experimental aortic aneurysm studies. Given the advances in our understanding of molecular mechanisms triggering aortic dilatation and dissection, individualized management tailored to the underlying genetic defect may be on the horizon of individualized medicine. We anticipate that ongoing research will address the question whether such genotype/pathogenesis-driven treatments can replace current phenotype/syndrome-driven strategies and whether other forms of aortopathies should be treated similarly. In this work, we review currently used and promising medical treatment options for patients with heritable aortic aneurysmal disorders. PMID:24527681

Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.

PubMed

Guo, Dong-chuan; Regalado, Ellen; Casteel, Darren E; Santos-Cortez, Regie L; Gong, Limin; Kim, Jeong Joo; Dyack, Sarah; Horne, S Gabrielle; Chang, Guijuan; Jondeau, Guillaume; Boileau, Catherine; Coselli, Joseph S; Li, Zhenyu; Leal, Suzanne M; Shendure, Jay; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Kim, Choel; Milewicz, Dianna M

2013-08-08

Gene mutations that lead to decreased contraction of vascular smooth-muscle cells (SMCs) can cause inherited thoracic aortic aneurysms and dissections. Exome sequencing of distant relatives affected by thoracic aortic disease and subsequent Sanger sequencing of additional probands with familial thoracic aortic disease identified the same rare variant, PRKG1 c.530G>A (p.Arg177Gln), in four families. This mutation segregated with aortic disease in these families with a combined two-point LOD score of 7.88. The majority of affected individuals presented with acute aortic dissections (63%) at relatively young ages (mean 31 years, range 17-51 years). PRKG1 encodes type I cGMP-dependent protein kinase (PKG-1), which is activated upon binding of cGMP and controls SMC relaxation. Although the p.Arg177Gln alteration disrupts binding to the high-affinity cGMP binding site within the regulatory domain, the altered PKG-1 is constitutively active even in the absence of cGMP. The increased PKG-1 activity leads to decreased phosphorylation of the myosin regulatory light chain in fibroblasts and is predicted to cause decreased contraction of vascular SMCs. Thus, identification of a gain-of-function mutation in PRKG1 as a cause of thoracic aortic disease provides further evidence that proper SMC contractile function is critical for maintaining the integrity of the thoracic aorta throughout a lifetime. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Transfemoral aortic valve implantation in severe aortic stenosis patients with prior mitral valve prosthesis

PubMed Central

Sarı, Cenk; Baştuğ, Serdal; Kasapkara, Hacı Ahmet; Durmaz, Tahir; Keleş, Telat; Akçay, Murat; Aslan, Abdullah Nabi; Bayram, Nihal Akar; Bozkurt, Engin

2015-01-01

Introduction Transcatheter aortic valve implantation for severe symptomatic aortic stenosis in patients with a previous mitral valve prosthesis is technically challenging, and pre-procedural comprehensive assessment of these patients before transcatheter aortic valve implantation is vital for an uncomplicated and successful procedure. Aim We want to share our experience with transcatheter aortic valve implantation in patients with a preexisting functional mitral valve prosthesis and describe a series of important technical and pre-procedural details. Material and methods At our center, 135 patients with symptomatic severe aortic stenosis were treated with transcatheter aortic valve implantation. Six of them with a preexisting mitral valve prosthesis received an Edwards SAPIEN XT valve through the transfemoral route. Results Transcatheter aortic valve implantation was performed successfully in all 6 patients without any deformation of the cobalt-chromium/steel stents of the aortic valve bioprosthesis. Also no distortion or malfunction in the mitral valve prosthesis was observed after the procedure. There were no complications during the hospitalization period. Post-procedural echocardiography revealed no or mild aortic paravalvular regurgitation and normal valve function in all the patients. In addition, serial echocardiographic examination demonstrated that both the stability and function of the aortic and mitral prosthetic valves were normal without any deterioration in the gradients and the degree of the regurgitation at long-term follow-ups. Conclusions Our experience confirms that transcatheter aortic valve implantation is technically feasible in patients with previous mitral valve replacement but comprehensive evaluation of patients by multimodal imaging techniques such as transesophageal echocardiography and multislice computed tomography is mandatory for a successful and safe procedure. PMID:26677380

Association Between Gout and Aortic Stenosis

PubMed Central

Chang, Kevin; Yokose, Chio; Tenner, Craig; Oh, Cheongeun; Donnino, Robert; Choy-Shan, Alana; Pike, Virginia C.; Shah, Binita D.; Lorin, Jeffrey D.; Krasnokutsky, Svetlana; Sedlis, Steven P.; Pillinger, Michael H.

2017-01-01

Background An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. Methods We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. Results Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and non-aortic stenosis controls (n=224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n=24) of aortic stenosis subjects compared with 12.5% (n=28) of controls (unadjusted OR 1.90, 95% CI 1.05–3.48, p=0.038). Multivariate analysis retained significance only for gout (adjusted OR 2.08, 95% CI 1.00–4.32, p=0.049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs. 75.8 ± 1.0 years old, p=0.16). Conclusions Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications. PMID:27720853

A Hybrid Windkessel Model of Blood Flow in Arterial Tree Using Velocity Profile Method

NASA Astrophysics Data System (ADS)

Aboelkassem, Yasser; Virag, Zdravko

2016-11-01

For the study of pulsatile blood flow in the arterial system, we derived a coupled Windkessel-Womersley mathematical model. Initially, a 6-elements Windkessel model is proposed to describe the hemodynamics transport in terms of constant resistance, inductance and capacitance. This model can be seen as a two compartment model, in which the compartments are connected by a rigid pipe, modeled by one inductor and resistor. The first viscoelastic compartment models proximal part of the aorta, the second elastic compartment represents the rest of the arterial tree and aorta can be seen as the connection pipe. Although the proposed 6-elements lumped model was able to accurately reconstruct the aortic pressure, it can't be used to predict the axial velocity distribution in the aorta and the wall shear stress and consequently, proper time varying pressure drop. We then modified this lumped model by replacing the connection pipe circuit elements with a vessel having a radius R and a length L. The pulsatile flow motions in the vessel are resolved instantaneously along with the Windkessel like model enable not only accurate prediction of the aortic pressure but also wall shear stress and frictional pressure drop. The proposed hybrid model has been validated using several in-vivo aortic pressure and flow rate data acquired from different species such as, humans, dogs and pigs. The method accurately predicts the time variation of wall shear stress and frictional pressure drop. Institute for Computational Medicine, Dept. Biomedical Engineering.

Outcomes of Aortic Valve-Sparing Operations in Marfan Syndrome.

PubMed

David, Tirone E; David, Carolyn M; Manlhiot, Cedric; Colman, Jack; Crean, Andrew M; Bradley, Timothy

2015-09-29

In many cardiac units, aortic valve-sparing operations have become the preferred surgical procedure to treat aortic root aneurysm in patients with Marfan syndrome, based on relatively short-term outcomes. This study examined the long-term outcomes of aortic valve-sparing operations in patients with Marfan syndrome. All patients with Marfan syndrome operated on for aortic root aneurysm from 1988 through 2012 were followed prospectively for a median of 10 years. Follow-up was 100% complete. Time-to-event analyses were calculated using the Kaplan-Meier method with log-rank test for comparisons. A total of 146 patients with Marfan syndrome had aortic valve-sparing operations. Reimplantation of the aortic valve was performed in 121 and remodeling of the aortic root was performed in 25 patients. Mean age was 35.7 ± 11.4 years and two-thirds were men. Nine patients had acute, 2 had chronic type A, and 3 had chronic type B aortic dissections before surgery. There were 1 operative and 6 late deaths, 5 caused by complications of dissections. Mortality rate at 15 years was 6.8 ± 2.9%, higher than the general population matched for age and sex. Five patients required reoperation on the aortic valve: 2 for endocarditis and 3 for aortic insufficiency. Three patients developed severe, 4 moderate, and 3 mild-to-moderate aortic insufficiency. Rate of aortic insufficiency at 15 years was 7.9 ± 3.3%, lower after reimplantation than remodeling. Nine patients developed new distal aortic dissections during follow-up. Rate of dissection at 15 years was 16.5 ± 3.4%. Aortic valve-sparing operations in patients with Marfan syndrome were associated with low rates of valve-related complications in long-term follow-up. Residual and new aortic dissections were the leading cause of death. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Aortic Dissection in Patients With Bicuspid Aortic Valve–Associated Aneurysms

PubMed Central

Wojnarski, Charles M.; Svensson, Lars G.; Roselli, Eric E.; Idrees, Jay J.; Lowry, Ashley M.; Ehrlinger, John; Pettersson, Gösta B.; Gillinov, A. Marc; Johnston, Douglas R.; Soltesz, Edward G.; Navia, Jose L.; Hammer, Donald F.; Griffin, Brian; Thamilarasan, Maran; Kalahasti, Vidyasagar; Sabik, Joseph F.; Blackstone, Eugene H.; Lytle, Bruce W.

2016-01-01

Background Data regarding the risk of aortic dissection in patients with bicuspid aortic valve and large ascending aortic diameter are limited, and appropriate timing of prophylactic ascending aortic replacement lacks consensus. Thus our objectives were to determine the risk of aortic dissection based on initial cross-sectional imaging data and clinical variables and to isolate predictors of aortic intervention in those initially prescribed serial surveillance imaging. Methods From January 1995 to January 2014, 1,181 patients with bicuspid aortic valve underwent cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI) to ascertain sinus or tubular ascending aortic diameter greater than or equal to 4.7 cm. Random Forest classification was used to identify risk factors for aortic dissection, and among patients undergoing surveillance, time-related analysis was used to identify risk factors for aortic intervention. Results Prevalence of type A dissection that was detected by imaging or was found at operation or on follow-up was 5.3% (n = 63). Probability of type A dissection increased gradually at a sinus diameter of 5.0 cm—from 4.1% to 13% at 7.2 cm—and then increased steeply at an ascending aortic diameter of 5.3 cm—from 3.8% to 35% at 8.4 cm—corresponding to a cross-sectional area to height ratio of 10 cm2/m for sinuses of Valsalva and 13 cm2/m for the tubular ascending aorta. Cross-sectional area to height ratio was the best predictor of type A dissection (area under the curve [AUC] = 0.73). Conclusions Early prophylactic ascending aortic replacement in patients with bicuspid aortic valve should be considered at high-volume aortic centers to reduce the high risk of preventable type A dissection in those with aortas larger than approximately 5.0 cm or with a cross-sectional area to height ratio greater than approximately 10 cm2/m. PMID:26209494

Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms

PubMed Central

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Haertl, Felix; Matevossian, Edouard; Zernecke, Alma; Eckstein, Hans-Henning; Pelisek, Jaroslav

2014-01-01

Cysteine and aspartic proteases possess high elastolytic activity and might contribute to the degradation of the abdominal aortic aneurysm (AAA) wall. The aim of this study was to analyze, in detail, the proteases (cathepsins B, D, K, L and S, and inhibitor cystatin C) found in human AAA and healthy aortic tissue samples. The vessel walls from AAA patients (n=36) and nonaneurysmal aortae (n=10) were retrieved using conventional surgical repair and autopsy methods. Serum samples from the same AAA patients and 10 healthy volunteers were also collected. Quantitative expression analyses were performed at the mRNA level using real-time reverse transcriptase-PCR (RT–PCR). Furthermore, analyses at the protein level included western blot and immunoprecipitation analyses. Cellular sources of cysteine/aspartic proteases and cystatin C were identified by immunohistochemistry (IHC). All cysteine/aspartic proteases and cystatin C were detected in the AAA and control samples. Using quantitative RT–PCR, a significant increase in expression was observed for cathepsins B (P=0.021) and L (P=0.018), compared with the controls. Cathepsin B and cystatin C were also detected in the serum of AAA patients. Using IHC, smooth muscle cells (SMCs) and macrophages were positive for all of the tested cathepsins, as well as cystatin C; in addition, the lymphocytes were mainly positive for cathepsin B, followed by cathepsins D and S. All cysteine/aspartic proteases analyzed in our study were detected in the AAA and healthy aorta. The highest expression was found in macrophages and SMCs. Consequently, cysteine/aspartic proteases might play a substantial role in AAA. PMID:24833013

Mathematical, numerical and experimental study in the human aorta with coexisting models of bicuspid aortic stenosis and coarctation of the aorta.

PubMed

Keshavarz-Motamed, Z; Garcia, J; Kadem, L

2011-01-01

Coarctation of the aorta is an obstruction of the aorta and is usually associated with other concomitant cardiovascular abnormalities especially with bicuspid aortic valve stenosis. The objectives of this study are, (1) to investigate the effects of coarctation on the hemodynamics in the aorta to gain a better understanding of the cause of certain post-surgical coarctation problems, (2) to develop and introduce a new lumped parameter model, mainly based on non-invasive data, allowing the description of the interaction between left ventricle, coarctation of the aorta, aortic valve stenosis, and the arterial system.

Acellular vascular matrix grafts from human placenta chorion: Impact of ECM preservation on graft characteristics, protein composition and in vivo performance.

PubMed

Schneider, Karl H; Enayati, Marjan; Grasl, Christian; Walter, Ingrid; Budinsky, Lubos; Zebic, Gabriel; Kaun, Christoph; Wagner, Anja; Kratochwill, Klaus; Redl, Heinz; Teuschl, Andreas H; Podesser, Bruno K; Bergmeister, Helga

2018-05-29

Small diameter vascular grafts from human placenta, decellularized with either Triton X-100 (Triton) or SDS and crosslinked with heparin were constructed and characterized. Graft biochemical properties, residual DNA, and protein composition were evaluated to compare the effect of the two detergents on graft matrix composition and structural alterations. Biocompatibility was tested in vitro by culturing the grafts with primary human macrophages and in vivo by subcutaneous implantation of graft conduits (n = 7 per group) into the flanks of nude rats. Subsequently, graft performance was evaluated using an aortic implantation model in Sprague Dawley rats (one month, n = 14). In situ graft imaging was performed using MRI angiography. Retrieved specimens were analyzed by electromyography, scanning electron microscopy, histology and immunohistochemistry to evaluate cell migration and the degree of functional tissue remodeling. Both decellularization methods resulted in grafts of excellent biocompatibility in vitro and in vivo, with low immunogenic potential. Proteomic data revealed removal of cytoplasmic proteins with relative enrichment of ECM proteins in decelluarized specimens of both groups. Noteworthy, LC-Mass Spectrometry analysis revealed that 16 proteins were exclusively preserved in Triton decellularized specimens in comparison to SDS-treated specimens. Aortic grafts showed high patency rates, no signs of thrombus formation, aneurysms or rupture. Conduits of both groups revealed tissue-specific cell migration indicative of functional remodeling. This study strongly suggests that decellularized allogenic grafts from the human placenta have the potential to be used as vascular replacement materials. Both detergents produced grafts with low residual immunogenicity and appropriate mechanical properties. Observed differences in graft characteristics due to preservation method had no impact on successful in vivo performance in the rodent model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Applicability of fetal thoracic aortic diameter measurement in the prediction of birth weight in Holstein-Friesian cows - Short communication.

PubMed

Vincze, Boglárka; Gáspárdy, András; Kovács, Levente; Albert, Ervin; Kézér, Luca; Baska, Ferenc; Szenci, Ottó

2017-03-01

Transabdominal ultrasonography has been shown to be a useful and reliable method for assessing fetal well-being in horses and cattle. To test the applicability of fetal aortic diameter measurement in cattle, 44 late-term pregnant cows and heifers were examined 21 to 0 days prior to calving. Mean fetal aortic diameter was 2.07 ± 0.14 cm and mean fetal heart rate (FHR) was 109 ± 17 bpm. Three dead calves were dissected and their aortic diameter was measured in a water bath. The mean birth weight (n = 44) was 39.9 ± 5.8 kg. There was a significant negative correlation between FHR and fetal aortic diameter. However, although some studies have shown that fetal aortic diameter strongly correlates with birth weight in near-term horses and cattle, in this study there was no correlation between fetal aortic diameter and birth weight in Holstein-Friesian cows and heifers irrespective of whether the fetus was born alive or dead.

[Feasibility and possibility of Inoue stent graft for thoracic aortic aneurysms].

PubMed

Marui, Akira; Kimura, Takeshi; Tazaki, Junichi; Sakata, Ryuzo; Inoue, Kanji

2011-01-01

Open surgical repair is a traditional treatment for patients with thoracic aortic aneurysms. Despite recent advances in surgical techniques and anesthetic management, the surgical repair of thoracic aortic aneurysms is still associated with significant mortality and morbidity. Endovascular aneurysm repair of thoracic aortic aneurysms is emerging as an alternative method for repair in selected patients. Although endovascular stent grafting is less invasive than open surgical repair, involvement of branch vessels and precipitous curvature of the aortic arch limits the application of stent grafting. Inoue stent graft system consists of soft nitinol ring-type stent which enables very flexible stent graft, and it can well comply with the precipitous curvature of the aortic arch. The system also provides a stent graft with a side branch to manage the left subclavian artery. This system does not require the surgical revascularization of the left subclavian artery. In this report, we show the feasibility and possibility of Inoue stent graft system to manage the aortic arch aneurysm.

Comparison of an Oscillometric Method with Cardiac Magnetic Resonance for the Analysis of Aortic Pulse Wave Velocity

PubMed Central

Feistritzer, Hans-Josef; Reinstadler, Sebastian J.; Klug, Gert; Kremser, Christian; Seidner, Benjamin; Esterhammer, Regina; Schocke, Michael F.; Franz, Wolfgang-Michael; Metzler, Bernhard

2015-01-01

Objectives Pulse wave velocity (PWV) is the proposed gold-standard for the assessment of aortic elastic properties. The aim of this study was to compare aortic PWV determined by a recently developed oscillometric device with cardiac magnetic resonance imaging (CMR). Methods PWV was assessed in 40 volunteers with two different methods. The oscillometric method (PWVOSC) is based on a transfer function from the brachial pressure waves determined by oscillometric blood pressure measurements with a common cuff (Mobil-O-Graph, I.E.M. Stolberg, Germany). CMR was used to determine aortic PWVCMR with the use of the transit time method based on phase-contrast imaging at the level of the ascending and abdominal aorta on a clinical 1.5 Tesla scanner (Siemens, Erlangen, Germany). Results The median age of the study population was 34 years (IQR: 24–55 years, 11 females). A very strong correlation was found between PWVOSC and PWVCMR (r = 0.859, p < 0.001). Mean PWVOSC was 6.7 ± 1.8 m/s and mean PWVCMR was 6.1 ± 1.8 m/s (p < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 0.57 m/s (upper and lower limit of agreement: 2.49 m/s and -1.34 m/s). The corresponding coefficient of variation between both measurements was 15%. Conclusion Aortic pulse wave velocity assessed by transformation of the brachial pressure waveform showed an acceptable agreement with the CMR-derived transit time method. PMID:25612307

Mosaic partial deletion of PTPN12 in a child with interrupted aortic arch type A.

PubMed

Duffy, Elizabeth A; Pretorius, Pamela R; Lerach, Stephanie; Lohr, Jamie L; Hirsch, Betsy; Souza, Cleiton M; Veillette, André; Schimmenti, Lisa A

2015-11-01

Congenital heart malformations, including those of the great vessels, are among the most common human birth defects. The goal of this study was to identify the significance of a de novo mosaic PTPN12 partial deletion identified in a newborn with an interrupted aortic arch type A, ventricular septal defect, and pyloric stenosis. PTPN12, a downstream target of the RAS pathway, has a known role in endothelial cell adhesion and migration. Neither genetic nor genomic variants in PTPN12 have been described in a human patient; therefore, we evaluated the effect of ptpn12 in a mouse conditional knockout and zebrafish knockdown model to determine the significance of a loss in gene expression. Observed loss of ptpn12 expression in zebrafish resulted in abnormal branchial arch and tail vasculature patterns, with reduced blood flow throughout the animal. This phenotype was supported by anomalous vasculature in a conditional Ptpn12 mouse knockout. Given the novel co-occurrence of interrupted aortic arch type A, ventricular septal defect, and partial deletion of PTPN12 in the patient, as well as vascular phenotypes in Ptpn12 mouse and ptpn12 zebrafish models, it is likely that PTPN12 has a significant role in cardiovascular development and vessel formation during human embryonic development. Furthermore, the partial deletion of PTPN12 lead to interrupted aortic arch type A in this child and may represent a novel condition caused by a null mutation in the RAS pathway. © 2015 Wiley Periodicals, Inc.

Thrombogenic potential of transcatheter aortic valve implantation with trivial paravalvular leakage

PubMed Central

Siegel, Rolland

2014-01-01

Background Significant paravalvular leakage after transcatheter aortic valve implantation (TAVI) correlates with increased morbidity and mortality, but adverse consequences of trivial paravalvular leakage have stimulated few investigations. Using a unique method distinctly different from other diagnostic approaches, we previously reported elevated backflow velocities of short duration (transients) in mechanical valve closure. In this study, similar transients were found in a transcatheter valve paravalvular leakage avatar. Methods Paravalvular leakage rate (zero to 58 mL/second) and aortic valve incompetence (volumetric back flow/forward flow; zero to 32%) were made adjustable using a mock transcatheter aortic valve device and tested in quasi-steady and pulsatile flow test systems. Projected dynamic valve area (PDVA) from the back illuminated mock transcatheter aortic valve device was measured and regional backflow velocities were derived by dividing volumetric flow rate by the PDVA over the open and closing valve phase and the total closed valve area derived from backflow leakage. Results Aortic incompetence from 1-32% generated negative backflow transients from 8 to 267 meters/second, a range not dissimilar to that measured in mechanical valves with zero paravalvular leakage. Optimal paravalvular leakage was identified; not too small generating high backflow transients, not too large considering volume overload and cardiac energy loss caused by defective valve behavior and fluid motion. Conclusions Thrombogenic potential of transcatheter aortic valves with trivial aortic incompetence and high magnitude regional backflow velocity transients was comparable to mechanical valves. This may have relevance to stroke rate, asymptomatic microembolic episodes and indications for anticoagulation therapy after transcatheter valve insertion. PMID:25333018

Minimally Invasive Transverse Aortic Constriction in Mice.

PubMed

Zaw, Aung Moe; Williams, Connor M; Law, Helen K W; Chow, Billy Kwok Chong

2017-03-14

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Echocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome

PubMed Central

Selamet Tierney, Elif Seda; Levine, Jami C.; Chen, Shan; Bradley, Timothy J.; Pearson, Gail D.; Colan, Steven D.; Sleeper, Lynn A.; Campbell, M. Jay; Cohen, Meryl S.; Backer, Julie De; Guey, Lin T.; Heydarian, Haleh; Lai, Wyman W.; Lewin, Mark B.; Marcus, Edward; Mart, Christopher R.; Pignatelli, Ricardo H.; Printz, Beth F.; Sharkey, Angela M.; Shirali, Girish S.; Srivastava, Shubhika; Lacro, Ronald V.

2013-01-01

Background The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Methods Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area–adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmax Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Results Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R2 = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmax Z scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmax Z scores < 4.5. Conclusions The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility. PMID:23582510

Agreement between methods of measurement of mean aortic wall thickness by MRI.

PubMed

Rosero, Eric B; Peshock, Ronald M; Khera, Amit; Clagett, G Patrick; Lo, Hao; Timaran, Carlos

2009-03-01

To assess the agreement between three methods of calculation of mean aortic wall thickness (MAWT) using magnetic resonance imaging (MRI). High-resolution MRI of the infrarenal abdominal aorta was performed on 70 subjects with a history of coronary artery disease who were part of a multi-ethnic population-based sample. MAWT was calculated as the mean distance between the adventitial and luminal aortic boundaries using three different methods: average distance at four standard positions (AWT-4P), average distance at 100 automated positions (AWT-100P), and using a mathematical computation derived from the total vessel and luminal areas (AWT-VA). Bland-Altman plots and Passing-Bablok regression analyses were used to assess agreement between methods. Bland-Altman analyses demonstrated a positive bias of 3.02+/-7.31% between the AWT-VA and the AWT-4P methods, and of 1.76+/-6.82% between the AWT-100P and the AWT-4P methods. Passing-Bablok regression analyses demonstrated constant bias between the AWT-4P method and the other two methods. Proportional bias was, however, not evident among the three methods. MRI methods of measurement of MAWT using a limited number of positions of the aortic wall systematically underestimate the MAWT value compared with the method that calculates MAWT from the vessel areas. Copyright (c) 2009 Wiley-Liss, Inc.

Marfan syndrome, magnesium status and medical prevention of cardiovascular complications by hemodynamic treatments and antisense gene therapy.

PubMed

Igondjo-Tchen, S; Pagès, N; Bac, P; Godeau, G; Durlach, J

2003-03-01

The medical management of Marfan Syndrome (MFS) mainly relies on early prevention of the aortic complications. Hemodynamic treatments try to diminish the forcefulness of cardiac contractions and to reduce blood pressure: for example long term administration of propranolol may significantly reduce the rate of increase in aortic ratio (aortic diameter/expected aortic diameter). Retardation of aortic dilatation may be most often observed by early treatment started when the baseline end-diastolic aortic root diameter is < 40 mm. It seems better to use beta-blockers without intrinsic sympathomimetic activity. Successful acceptance of beta-blockers may be limited by side-effects, but the efficiency of alternative hypotensive agents (calcium channel inhibitors, ACE inhibitors) is not yet validated. Gene therapy might constitute an etiologic specific treatment of MFS. FBN1-RZ1 hammerhead antisense ribozyme is able to suppress expression of the mutant FBN1 allele. The use of ribozymes as systemic therapeutic agents will depend on efficient delivery to its target, but the various proposed vectors raise yet unsolved problems. A hydrogel angioplasty balloon might be a possible vector for delivering an antisense ribozyme in the aortic wall specifically. Ribozymes--as deoxyribonucleotides--may be taken up by tissue upon local application. Further research should study ex vivo local application of antisense ribozyme on human aortic wall, before assessing in vivo efficiency and tolerance of this aortic local vectorisation. It is always necessary to maintain a balanced magnesium intake in patients with MFS. Firstly to prevent the multiple noxious effects of magnesium deficiency on cardiovascular targets. Secondly to ensure the best efficiency and the least toxicity of the hemodynamic drugs used as long term prophylactic treatment for cardiovascular complications and of the etiologic antisense magnesium-dependent gene therapy, in the future.

Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

NASA Technical Reports Server (NTRS)

Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

2000-01-01

This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (P<0.01). A 50% increase in FGF-2 content versus control (P<0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

Hybrid endovascular repair in aortic arch pathologies: a retrospective study.

PubMed

Ma, Xiaohui; Guo, Wei; Liu, Xiaoping; Yin, Tai; Jia, Xin; Xiong, Jiang; Zhang, Hongpeng; Wang, Lijun

2010-11-18

The aortic arch presents specific challenges to endovascular repair. Hybrid repair is increasingly evolving as an alternative option for selected patients, and promising initial results have been reported. The aim of this study was to introduce our experiences and evaluate mid-term results of supra aortic transpositions for extended endovascular repair of aortic arch pathologies. From December 2002 to January 2008, 25 patients with thoracic aortic aneurysms and dissections involving the aortic arch were treated with hybrid endovascular treatment in our center. Of the 25 cases, 14 were atherosclerotic thoracic aortic aneurysms and 11 were thoracic aortic dissection. The hybrid repair method included total-arch transpositions (15 cases) or hemi-arch transpositions (10 cases), and endovascular procedures. All hybrid endovascular procedures were completed successfully. Three early residual type-I endoleaks and one type-II endoleak were observed. Stroke occurred in three patients (8%) during the in-hospital stage. The perioperative mortality rate was 4%; one patients died post-operatively from catheter related complications. The average follow-up period was 15 ± 5.8 months (range, 1-41 months). The overall crude survival rate at 15 months was 92% (23/25). During follow-up, new late endoleaks and stent-raft related complications were not observed. One case (4%) developed a unilateral lower limb deficit at 17 days and was readmitted to hospital. In conclusion, the results are encouraging for endovascular aortic arch repair in combination with supra-aortic transposition in high risk cases. Aortic endografting offers good mid-term results. Mid-term results of the hybrid approach in elderly patients with aortic arch pathologies are satisfying.

Associations of Age and Sex with Marfan Phenotype: The NHLBI GenTAC Registry

PubMed Central

Roman, Mary J.; Devereux, Richard B.; Preiss, Liliana R.; Asch, Federico M.; Eagle, Kim A.; Holmes, Kathryn W.; LeMaire, Scott A.; Maslen, Cheryl L.; Milewicz, Dianna M.; Morris, Shaine A.; Prakash, Siddharth K.; Pyeritz, Reed E.; Ravekes, William J.; Shohet, Ralph V.; Song, Howard K.; Weinsaft, Jonathan W.

2017-01-01

Background The associations of age and sex with phenotypic features of Marfan syndrome have not been systematically examined in a large cohort of both children and adults. Methods and Results We evaluated 789 Marfan patients enrolled in the NHLBI GenTAC Registry (53% male; mean age 31 [range: 1–86 years]). Females aged≥15 and males aged≥16 years were considered adults based on average age of skeletal maturity. Adults (n=606) were more likely than children (n=183) likely to have spontaneous pneumothorax, scoliosis, and striae, but were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalence of aortic root dilatation. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood vs. adulthood (2 vs. 35% and 1 vs. 9%, respectively, both p<0.0001). Adult males were more likely than females to have aortic root dilatation (92 vs. 84%), aortic regurgitation (55 vs. 36%) and to have undergone prophylactic aortic root replacement (47 vs. 24%), all p<0.001. Prevalence of prior aortic dissection tended to be higher in males than females (25 vs. 18%, p=0.06); 44% of dissections were type B. Type B dissection was strongly associated with previous prophylactic aortic root replacement. Conclusions Pulmonary, skeletal and aortic complications, but not other phenotypic features, are more prevalent in adults than children in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. Aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially in men and following previous prophylactic aortic root replacement. PMID:28600386

No Beneficial Effect of General and Specific Anti-Inflammatory Therapies on Aortic Dilatation in Marfan Mice

PubMed Central

den Hartog, Alexander W.; Radonic, Teodora; de Vries, Carlie J. M.; Zwinderman, Aeilko H.; Groenink, Maarten; Mulder, Barbara J. M.; de Waard, Vivian

2014-01-01

Aims Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. In the FBN1 C1039G/+ Marfan mouse model, losartan decreases aortic root dilatation. We recently confirmed this beneficial effect of losartan in adult patients with Marfan syndrome. The straightforward translation of this mouse model to man is reassuring to test novel treatment strategies. A number of studies have shown signs of inflammation in aortic tissue of Marfan patients. This study examined the efficacy of anti-inflammatory therapies in attenuating aortic root dilation in Marfan syndrome and compared effects to the main preventative agent, losartan. Methods and Results To inhibit inflammation in FBN1 C1039G/+ Marfan mice, we treated the mice with losartan (angiotensin II receptor type 1 inhibitor), methylprednisolone (corticosteroid) or abatacept (T-cell-specific inhibitor). Treatment was initiated in adult Marfan mice with already existing aortic root dilatation, and applied for eight weeks. Methylprednisolone- or abatacept-treated mice did not reveal a reduction in aortic root dilatation. In this short time frame, losartan was the only treatment that significantly reduced aorta inflammation, transforming growth factor-beta (TGF-β) signaling and aortic root dilatation rate in these adult Marfan mice. Moreover, the methylprednisolone-treated mice had significantly more aortic alcian blue staining as a marker for aortic damage. Conclusion Anti-inflammatory agents do not reduce the aortic dilatation rate in Marfan mice, but possibly increase aortic damage. Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling. PMID:25238161

Update on the prevention of death from ruptured abdominal aortic aneurysm.

PubMed

Jacomelli, Jo; Summers, Lisa; Stevenson, Anne; Lees, Tim; Earnshaw, Jonothan J

2017-09-01

Objectives To monitor the early effect of a national population screening programme for abdominal aortic aneurysm in 65-year-old men. Setting The study used national statistics for death rates from abdominal aortic aneurysm (Office of National Statistics) and hospital admission data in England (Hospital Episode Statistics). Methods Information concerning deaths from abdominal aortic aneurysm (ruptured and non-ruptured) (1999-2014) and hospital admissions for ruptured abdominal aortic aneurysm (2000-2015) was examined. Results The absolute number of deaths from abdominal aortic aneurysm in men and women aged 65 and over has decreased by around 30% from 2001 to 2014, but as the population has increased, the relative reduction was 45.6% and 40.0%, respectively. Some 65% of all abdominal aortic aneurysm deaths are in men aged over 65; women aged 65 and over account for around 31%. Deaths from ruptured abdominal aortic aneurysm in men aged 60-74 (the screened group) appear to be declining at the same rate as in men aged 75 and over. The relative decline in admissions to hospital with ruptured abdominal aortic aneurysm may be greater in men and women aged 60-74 (which contains the screened group of men), than those older, giving the first possible evidence that abdominal aortic aneurysm screening is having an effect. Conclusion The death rate from abdominal aortic aneurysm is declining rapidly in England. There is the first evidence that screening may be contributing to this reduction.

Genetic Bases of Bicuspid Aortic Valve: The Contribution of Traditional and High-Throughput Sequencing Approaches on Research and Diagnosis.

PubMed

Giusti, Betti; Sticchi, Elena; De Cario, Rosina; Magi, Alberto; Nistri, Stefano; Pepe, Guglielmina

2017-01-01

Bicuspid aortic valve (BAV) is a common (0.5-2.0% of general population) congenital heart defect with increased prevalence of aortic dilatation and dissection. BAV has an autosomal dominant inheritance with reduced penetrance and variable expressivity. BAV has been described as an isolated trait or associated with syndromic conditions [e.g., Marfan Marfan syndrome or Loeys-Dietz syndrome (MFS, LDS)]. Identification of a syndromic condition in a BAV patient is clinically relevant to personalize aortic surgery indication. A 4-fold increase in BAV prevalence in a large cohort of unrelated MFS patients with respect to general population was reported, as well as in LDS patients (8-fold). It is also known that BAV is more frequent in patients with thoracic aortic aneurysm (TAA) related to mutations in ACTA2, FBN1 , and TGFBR2 genes. Moreover, in 8 patients with BAV and thoracic aortic dilation, not fulfilling the clinical criteria for MFS, FBN1 mutations in 2/8 patients were identified suggesting that FBN1 or other genes involved in syndromic conditions correlated to aortopathy could be involved in BAV. Beyond loci associated to syndromic disorders, studies in humans and animal models evidenced/suggested the role of further genes in non-syndromic BAV. The transcriptional regulator NOTCH1 has been associated with the development and acceleration of calcium deposition. Genome wide marker-based linkage analysis demonstrated a linkage of BAV to loci on chromosomes 18, 5, and 13q. Recently, a role for GATA4 / 5 in aortic valve morphogenesis and endocardial cell differentiation has been reported. BAV has also been associated with a reduced UFD1L gene expression or involvement of a locus containing AXIN1 / PDIA2 . Much remains to be understood about the genetics of BAV. In the last years, high-throughput sequencing technologies, allowing the analysis of large number of genes or entire exomes or genomes, progressively became available. The latter issue together with the development of "BigData" analysis methods improving their interpretation and integration with clinical data represents a promising opportunity to increase the disease knowledge and diagnosis in monogenic and multifactorial complex traits. This review summarized the main knowledge on the BAV genetic bases, the role of genetic diagnosis in BAV patient managements and the crucial challenges for the comprehension of genetics of BAV in research and diagnosis.

[Anesthesia for total and descending aorta replacement and aortic valve replacement for post-repair aneurysm of coarctation of aorta and aortic stenosis].

PubMed

Furuichi, Yuko; Shimizu, Jun; Sakamoto, Atsuhiro

2012-04-01

We experienced anesthesia for total arch and descending aorta replacement and aortic valve replacement for post-repair aneurysm of coarctation of aorta and aortic stenosis. Because there was possibility that post coarctectomy syndrome would occur after repair of coarctation of aorta, administration of depressor that acts on renin-angiotensin-aldosterone and careful observation were needed postoperatively. In consideration of the development of collateral vessels, preoperative imaging evaluation was added and operative method in cardiopulmonary bypass was adjusted. Careful preoperative evaluation is very important in cardiac anesthesia.

Hemodynamics in an Aorta with Bicuspid and Trileaflet Valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2015-11-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as ascending aortic aneurysm, aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. Two main hypotheses - the genetic and the hemodynamic are discussed in literature to explain the development and progression of aortopathies in patients with BAV. In this study we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the Curvilinear Immersed Boundary (CURVIB) method coupled with an efficient thin-shell finite element (TS-FE) formulation for tissues to carry out fluid-structure interaction simulations of a healthy tri-leaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large scale flow patterns in the ascending aorta; and the shear stress magnitude on the aortic wall. The computed results are in qualitative agreement with in vivo Magnetic Resonance Imaging (MRI) data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation. This work is supported by the Lillehei Heart Institute at the University of Minnesota and the Minnesota Supercomputing Institute.

Use of fascia-peritoneum patch as a pledget for an infected aortic stump.

PubMed

Sarac, Timur P; Augustinos, Peter; Lyden, Sean; Ouriel, Kenneth

2003-12-01

Treatment of aortic prosthetic graft infections remains a challenge. One frequently encountered technical difficulty when removing an infected prosthetic aortic graft is how to close a short, friable remnant aortic stump. We present three case reports in which we used a layer of posterior rectus fascia-peritoneum to bolster oversewing a short infected aortic stump after removal of an infected aortic graft. All three patients underwent staged extra-anatomic axillary-to-femoral artery bypass procedures, with subsequent removal of the infected aortic graft as a second operation. Two of the three procedures were semi-elective, and one was done urgently because of a recurrent aortoenteric fistula. All three patients had less than 1 cm of remaining aortic neck below the renal arteries for closure. In each instance a segment of autogenous posterior rectus fascia-peritoneum was harvested and used as a circumferential pledget to bolster the anastomosis. No patient had stump blowout, and in no case was there computed tomography evidence of aneurysmal enlargement of the stump with follow-up of 12 and 24 months in two of the three survivors. Use of autogenous fascia-peritoneum is a durable and effective method to assist stump closure and prevent stump blowout after removal of infected aortic grafts.

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo

PubMed Central

Huk, Danielle J.; Hammond, Harriet L.; Kegechika, Hiroyuki; Lincoln, Joy

2013-01-01

Objective Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY-transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo, and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Methods and Results Using a combination of approaches, we defined CAVD pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RAR and RXR receptors. Conclusions Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of CAVD in the human population. PMID:23202364

Determination of oxidation state of iron in normal and pathologically altered human aortic valves

NASA Astrophysics Data System (ADS)

Czapla-Masztafiak, J.; Lis, G. J.; Gajda, M.; Jasek, E.; Czubek, U.; Bolechała, F.; Borca, C.; Kwiatek, W. M.

2015-12-01

In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe3+ is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe3+ form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

Micromanaging Abdominal Aortic Aneurysms

PubMed Central

Maegdefessel, Lars; Spin, Joshua M.; Adam, Matti; Raaz, Uwe; Toh, Ryuji; Nakagami, Futoshi; Tsao, Philip S.

2013-01-01

The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to “fine tune” the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility. PMID:23852016

INCLUDING AORTIC VALVE MORPHOLOGY IN COMPUTATIONAL FLUID DYNAMICS SIMULATIONS: INITIAL FINDINGS AND APPLICATION TO AORTIC COARCTATION

PubMed Central

Wendell, David C.; Samyn, Margaret M.; Cava, Joseph R.; Ellwein, Laura M.; Krolikowski, Mary M.; Gandy, Kimberly L.; Pelech, Andrew N.; Shadden, Shawn C.; LaDisa, John F.

2012-01-01

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. PMID:22917990

Haemodynamic outcome at four-dimensional flow magnetic resonance imaging following valve-sparing aortic root replacement with tricuspid and bicuspid valve morphology

PubMed Central

Semaan, Edouard; Markl, Michael; Chris Malaisrie, S.; Barker, Alex; Allen, Bradley; McCarthy, Patrick; Carr, James C.; Collins, Jeremy D.

2014-01-01

OBJECTIVE To provide a more complete characterization of aortic blood flow in patients following valve-sparing aortic root replacement (VSARR) compared with presurgical cohorts matched by tricuspid and bicuspid valve morphology, age and presurgical aorta size. METHODS Four-dimensional (4D) flow magnetic resonance imaging (MRI) was performed to analyse three-dimensional (3D) blood flow in the thoracic aorta of n = 13 patients after VSARR with reimplantation of native tricuspid aortic valve (TAV, n = 6) and bicuspid aortic valve (BAV, n = 7). Results were compared with presurgical age and aortic size-matched control cohorts with TAV (n = 10) and BAV (n = 10). Pre- and post-surgical aortic flow was evaluated using time-resolved 3D pathlines using a blinded grading system (0–2, 0 = small, 1 = moderate and 2 = prominent) analysing ascending aortic (AAo) helical flow. Systolic flow profile uniformity in the aortic root, proximal and mid-AAo was evaluated using a four-quadrant model. Further analysis in nine analysis planes distributed along the thoracic aorta quantified peak systolic velocity, retrograde fraction and peak systolic flow acceleration. RESULTS Pronounced AAo helical flow in presurgical control subjects (both BAV and TAV: helix grading = 1.8 ± 0.4) was significantly reduced (0.2 ± 0.4, P < 0.001) in cohorts after VSARR independent of aortic valve morphology. Presurgical AAo flow was highly eccentric for BAV patients but more uniform for TAV. VSARR resulted in less eccentric flow profiles. Systolic peak velocities were significantly (P < 0.05) increased in post-root repair BAV patients throughout the aorta (six of nine analysis planes) and to a lesser extent in TAV patients (three of nine analysis planes). BAV reimplantation resulted in significantly increased peak velocities in the proximal AAo compared with root repair with TAV (2.3 ± 0.6 vs 1.6 ± 0.4 m/s, P = 0.017). Post-surgical patients showed a non-significant trend towards higher systolic flow acceleration as a surrogate measure of reduced aortic compliance. CONCLUSIONS VSARR restored a cohesive flow pattern independent of native valve morphology but resulted in increased peak velocities throughout the aorta. 4D flow MRI methods can assess the clinical implications of altered aortic flow dynamics in patients undergoing VSARR. PMID:24317086

Abnormal aortic arch morphology in Turner syndrome patients is a risk factor for hypertension.

PubMed

De Groote, Katya; Devos, Daniël; Van Herck, Koen; Demulier, Laurent; Buysse, Wesley; De Schepper, Jean; De Wolf, Daniël

2015-09-01

Hypertension in Turner syndrome (TS) is a multifactorial, highly prevalent and significant problem that warrants timely diagnosis and rigorous treatment. The objective of this study was to investigate the association between abnormal aortic arch morphology and hypertension in adult TS patients. This was a single centre retrospective study in 74 adult TS patients (age 29.41 ± 8.91 years) who underwent a routine cardiac MRI. Patients were assigned to the hypertensive group (N = 31) if blood pressure exceeded 140/90 mmHg and/or if they were treated with antihypertensive medication. Aortic arch morphology was evaluated on MRI images and initially assigned as normal (N = 54) or abnormal (N = 20), based on the curve of the transverse arch and the distance between the left common carotid-left subclavian artery. We additionally used a new more objective method to describe aortic arch abnormality in TS by determination of the relative position of the highest point of the transverse arch (AoHP). Logistic regression analysis showed that hypertension is significantly and independently associated with age, BMI and abnormal arch morphology, with a larger effect size for the new AoHP method than for the classical method. TS patients with hypertension and abnormal arch morphology more often had dilatation of the ascending aorta. There is a significant association between abnormal arch morphology and hypertension in TS patients, independent of age and BMI, and not related to other structural heart disease. We suggest that aortic arch morphology should be included in the risk stratification for hypertension in TS and propose a new quantitative method to express aortic arch morphology.

A method for determining haploid and triploid genotypes and their association with vascular phenotypes in Williams syndrome and 7q11.23 duplication syndrome.

PubMed

Gregory, Michael D; Kolachana, Bhaskar; Yao, Yin; Nash, Tiffany; Dickinson, Dwight; Eisenberg, Daniel P; Mervis, Carolyn B; Berman, Karen F

2018-04-04

Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles. Haploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7. Commonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms.

Quantification of abdominal aortic deformation after EVAR

NASA Astrophysics Data System (ADS)

Demirci, Stefanie; Manstad-Hulaas, Frode; Navab, Nassir

2009-02-01

Quantification of abdominal aortic deformation is an important requirement for the evaluation of endovascular stenting procedures and the further refinement of stent graft design. During endovascular aortic repair (EVAR) treatment, the aortic shape is subject to severe deformation that is imposed by medical instruments such as guide wires, catheters, and, the stent graft. This deformation can affect the flow characteristics and morphology of the aorta which have been shown to be elicitors for stent graft failures and be reason for reappearance of aneurysms. We present a method for quantifying the deformation of an aneurysmatic aorta imposed by an inserted stent graft device. The outline of the procedure includes initial rigid alignment of the two abdominal scans, segmentation of abdominal vessel trees, and automatic reduction of their centerline structures to one specified region of interest around the aorta. This is accomplished by preprocessing and remodeling of the pre- and postoperative aortic shapes before performing a non-rigid registration. We further narrow the resulting displacement fields to only include local non-rigid deformation and therefore, eliminate all remaining global rigid transformations. Finally, deformations for specified locations can be calculated from the resulting displacement fields. In order to evaluate our method, experiments for the extraction of aortic deformation fields are conducted on 15 patient datasets from endovascular aortic repair (EVAR) treatment. A visual assessment of the registration results and evaluation of the usage of deformation quantification were performed by two vascular surgeons and one interventional radiologist who are all experts in EVAR procedures.

A geometric approach to aortic root surgical anatomy.

PubMed

Contino, Monica; Mangini, Andrea; Lemma, Massimo Giovanni; Romagnoni, Claudia; Zerbi, Pietro; Gelpi, Guido; Antona, Carlo

2016-01-01

The aim of this study was the analysis of the geometrical relationships between the different structures constituting the aortic root, with particular attention to interleaflet triangles, haemodynamic ventriculo-arterial junction and functional aortic annulus in normal subjects. Sixteen formol-fixed human hearts with normal aortic roots were studied. The aortic root was isolated, sectioned at the midpoint of the non-coronary sinus, spread apart and photographed by a high-resolution digital camera. After calibration and picture resizing, the software AutoCAD 2004 was used to identify and measure all the elements of the interleaflets triangles and of the aortic root that were objects of our analysis. Multiple comparisons were performed with one-way analysis of variance for continuous data and with Kruskal-Wallis analysis for non-continuous data. Linear regression and Pearson's product correlation were used to correlate root element dimensions when appropriate. Student's t-test was used to compare means for unpaired data. Heron's formula was applied to estimate the functional aortic annular diameters. The non coronary-left coronary interleaflets triangles were larger, followed by inter-coronary and right-non-coronary ones. The apical angle is <60° and its standard deviation can be considered an asymmetry index. The sinu-tubular junction was shown to be 10% larger than the virtual basal ring (VBR). The mathematical relationship between the haemodynamic ventriculo-arterial junction and the VBR calculated by linear regression and expressed in terms of the diameter was: haemodynamic ventriculo-arterial junction = 2.29 VBR (diameter) + 47. Conservative aortic surgery is based on a better understanding of aortic root anatomy and physiology. The relationships among its elements are of paramount importance during aortic valve repair/sparing procedures and they can be useful also in echocardiographic analysis and in computed tomography reconstruction. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow

NASA Technical Reports Server (NTRS)

Papadaki, M.; Tilton, R. G.; Eskin, S. G.; McIntire, L. V.

1998-01-01

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

3D Printing Based on Cardiac CT Assists Anatomic Visualization Prior to Transcatheter Aortic Valve Replacement

PubMed Central

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K.; Goncalves, Alexandra; Di Carli, Marcelo F.; Rybicki, Frank J.; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2017-01-01

Background 3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. Objective To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). Methods This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Results Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of −0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Conclusions Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. PMID:26732862

Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve

PubMed Central

Rueda-Martínez, Carmen; Fernández, M. Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

2016-01-01

Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180–240 days old) and 56 old (300–440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta. PMID:27711171

Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

PubMed

Rueda-Martínez, Carmen; Fernández, M Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

2016-01-01

Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240 days old) and 56 old (300-440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

Computational analysis of an aortic valve jet

NASA Astrophysics Data System (ADS)

Shadden, Shawn C.; Astorino, Matteo; Gerbeau, Jean-Frédéric

2009-11-01

In this work we employ a coupled FSI scheme using an immersed boundary method to simulate flow through a realistic deformable, 3D aortic valve model. This data was used to compute Lagrangian coherent structures, which revealed flow separation from the valve leaflets during systole, and correspondingly, the boundary between the jet of ejected fluid and the regions of separated, recirculating flow. Advantages of computing LCS in multi-dimensional FSI models of the aortic valve are twofold. For one, the quality and effectiveness of existing clinical indices used to measure aortic jet size can be tested by taking advantage of the accurate measure of the jet area derived from LCS. Secondly, as an ultimate goal, a reliable computational framework for the assessment of the aortic valve stenosis could be developed.

[Calcified aortic stenosis due to healed experimental bacterial endocarditis].

PubMed

Contreras Rodríguez, R; Rodríguez Velasco, A; Flores Miranda, J R; Ramos Amaro, J

1993-01-01

We studied the role of bacterial endocarditis in the development of aortic valve stenosis. A femoral arterio venous shunt was performed in nine dogs with the method previously proposed by Lillehei. We induced bacteremic infection with the administration of streptococcus mitis (1 x 10(10)) 10 ml once a day for 15 days these bacterium were sensible to penicillin. All dogs were treated with 1,000,000 U of benzatinic penicillin and sacrificed between 28-102 days after the bacterial inoculation ended. In one dog we observed bacterial endocarditis in the mitral and aortic valves and in other three dogs there was an aortic valve stenosis with calcium deposits in the body and in the free edges of the aortic valve with evident irregular stenosis as seen in man.

Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ran; Xie, Jun; Wu, Han

Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4more » protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular angiogenesis in db/db mice.« less

Anatomy of the nerves and ganglia of the aortic plexus in males

PubMed Central

Beveridge, Tyler S; Johnson, Marjorie; Power, Adam; Power, Nicholas E; Allman, Brian L

2015-01-01

It is well accepted that the aortic plexus is a network of pre- and post-ganglionic nerves overlying the abdominal aorta, which is primarily involved with the sympathetic innervation to the mesenteric, pelvic and urogenital organs. Because a comprehensive anatomical description of the aortic plexus and its connections with adjacent plexuses are lacking, these delicate structures are prone to unintended damage during abdominal surgeries. Through dissection of fresh, frozen human cadavers (n = 7), the present study aimed to provide the first complete mapping of the nerves and ganglia of the aortic plexus in males. Using standard histochemical procedures, ganglia of the aortic plexus were verified through microscopic analysis using haematoxylin & eosin (H&E) and anti-tyrosine hydroxylase stains. All specimens exhibited four distinct sympathetic ganglia within the aortic plexus: the right and left spermatic ganglia, the inferior mesenteric ganglion and one previously unidentified ganglion, which has been named the prehypogastric ganglion by the authors. The spermatic ganglia were consistently supplied by the L1 lumbar splanchnic nerves and the inferior mesenteric ganglion and the newly characterized prehypogastric ganglion were supplied by the left and right L2 lumbar splanchnic nerves, respectively. Additionally, our examination revealed the aortic plexus does have potential for variation, primarily in the possibility of exhibiting accessory splanchnic nerves. Clinically, our results could have significant implications for preserving fertility in men as well as sympathetic function to the hindgut and pelvis during retroperitoneal surgeries. PMID:25382240

The aortic ring model of angiogenesis: a quarter century of search and discovery

PubMed Central

Nicosia, R F

2009-01-01

The aortic ring model has become one of the most widely used methods to study angiogenesis and its mechanisms. Many factors have contributed to its popularity including reproducibility, cost effectiveness, ease of use and good correlation with in vivo studies. In this system aortic rings embedded in biomatrix gels and cultured under chemically defined conditions generate arborizing vascular outgrowths which can be stimulated or inhibited with angiogenic regulators. Originally based on the rat aorta, the aortic ring model was later adapted to the mouse for the evaluation of specific molecular alterations in genetically modified animals. Viral transduction of the aortic rings has enabled investigators to overexpress genes of interest in the aortic cultures. Experiments on angiogenic mechanisms have demonstrated that formation of neovessels in aortic cultures is regulated by macrophages, pericytes and fibroblasts through a complex molecular cascade involving growth factors, inflammatory cytokines, axonal guidance cues, extracellular matrix (ECM) molecules and matrix-degrading proteolytic enzymes. These studies have shown that endothelial sprouting can be effectively blocked by depleting the aortic explants of macrophages or by interfering with the angiogenic cascade at multiple levels including growth factor signalling, cell adhesion and proteolytic degradation of the ECM. In this paper, we review the literature in this field and retrace the journey from our first morphological descriptions of the aortic outgrowths to the latest breakthroughs in the cellular and molecular regulation of aortic vessel growth and regression. PMID:19725916

Echocardiographic Assessment of Aortic Pulse-Wave Velocity: Validation against Invasive Pressure Measurements.

PubMed

Styczynski, Grzegorz; Rdzanek, Adam; Pietrasik, Arkadiusz; Kochman, Janusz; Huczek, Zenon; Sobieraj, Piotr; Gaciong, Zbigniew; Szmigielski, Cezary

2016-11-01

Aortic pulse-wave velocity (PWV) is a measure of aortic stiffness that has a prognostic role in various diseases and in the general population. A number of methods are used to measure PWV, including Doppler ultrasound. Although echocardiography has been used for PWV measurement, to the authors' knowledge, it has never been tested against an invasive reference method at the same time point. Therefore, the aim of this study was to compare prospectively an echocardiographic PWV measurement, called echo-PWV, with an invasive study. Forty-five patients (mean age, 66 years; 60% men) underwent simultaneous intra-arterial pressure recording and echocardiographic Doppler flow evaluation during elective cardiac catheterization. Proximal pressure and Doppler waveforms were acquired in the aortic arch. Distal pressure waveforms were registered in the right and distal Doppler waveforms in the left external iliac artery. Transit time was measured as a delay of the foot of pressure or Doppler waveform in the distal relative to the proximal location. Distance was measured on the catheter for invasive PWV and over the surface for echo-PWV. Echo-PWV was calculated as distance divided by transit time. In the whole group, mean invasive PWV was 9.38 m/sec and mean echo-PWV was 9.51 m/sec (P = .78). The Pearson' correlation coefficient between methods was 0.93 (P < .0001). A Bland-Altman plot revealed a mean difference between invasive PWV and echo-PWV of 0.13 ± 0.79 m/sec. Echo-PWV, based on Doppler echocardiography, is a reliable method of aortic PWV measurement, with a close correlation with invasive assessment. Wider implementation of the echo-PWV method for the evaluation of aortic wall stiffness can further expand the clinical and scientific utility of echocardiography. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Trans-catheter aortic valve implantation after previous aortic homograft surgery.

PubMed

Drews, Thorsten; Pasic, Miralem; Buz, Semih; Unbehaun, Axel

2011-12-01

In patients with previous heart surgery, the operative risk is elevated during conventional aortic valve re-operations. Trans-catheter aortic valve implantation is a new method for the treatment of high-risk patients. Nevertheless, this new procedure carries potential risks in patients with previous homograft implantation in aortic position. Between April 2008 and February 2011, 345 consecutive patients (mean EuroSCORE (European System for Cardiac Operative Risk Evaluation): 38 ± 20%; mean Society of Thoracic Surgeons (STS) Mortality Score: 19 ± 16%; mean age: 80 ± 8 years; 111 men and 234 women) underwent trans-apical aortic valve implantation. In three patients, previous aortic homograft implantation had been performed. Homograft degeneration causing combined valve stenosis and incompetence made re-operation necessary. In all three patients, the aortic valve could be implanted using the trans-apical approach, and the procedure was successful. In two patients, there was slight paravalvular leakage of the aortic prosthesis and the other patient had slight central leakage. Neither ostium obstruction nor mitral valve damage was observed. Trans-catheter valve implantation can be performed successfully after previous homograft implantation. Particular care should be taken to achieve optimal valve positioning, not to obstruct the ostium of the coronary vessels due to the changed anatomic situation and not to cause annulus rupture. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus.

PubMed

Mosch, Josephin; Gleissner, Christian A; Body, Simon; Aikawa, Elena

2017-03-01

Calcific aortic valve disease (CAVD) is the most common valvular heart disease and likely evolves from inflammatory pre-conditions in the valve. Type II diabetes mellitus (DMII) has been associated with pathogenesis of CAVD, however, the mechanism initiating CAVD in DMII is not well understood and the human valve pathology in DMII has not been described. We therefore performed quantitative histological analyses of aortic valves of CAVD patients with and without DMII. CAVD human aortic valves (n=45) obtained after surgical valve replacement were examined macroscopically with gross measurements of calcified areas. Inflammation and calcification were assessed by immunohistochemistry and immunofluorescence staining. Calcification was increased in diabetic patients according to gross measurements (p<0.01) and alizarin red staining (p=0.05). Early calcification markers, including Runx2 (p=0.02) and alkaline phosphatase (ALP, p=0.03) were significantly elevated in diabetic patients. Furthermore, in diabetic patients we found significantly increased expression of annexin II (p=0.04) and annexin V (p=0.04), both of which are thought to play a role in microcalcification formation via apoptosis or extracellular vesicle release. Macrophage numbers were comparable in both groups (p=0.41), while the expression of the pro-inflammatory protein S100A9 (p<0.01) was significantly decreased in diabetic individuals. Evaluation of lymphocytes revealed similar CD8 (p=0.45) and CD4 (p=0.92) T cell counts in diabetic and non-diabetic aortic valves. Aortic valves from diabetic patients show more calcification, while inflammation is similar in both patient populations. Considering the generally accepted theory of an inflammation-dependent mechanism of calcification, these data suggest that in patients with CAVD requiring valve replacement, diabetic patients could be molecularly in a more advanced disease stage with a higher grade of mineralization than non-diabetic patients.

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea.

PubMed

García-Arredondo, Alejandro; Rojas-Molina, Alejandra; Ibarra-Alvarado, César; Lazcano-Pérez, Fernando; Arreguín-Espinosa, Roberto; Sánchez-Rodríguez, Judith

2016-01-01

Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa , Porites astreoides and Siderastrea siderea , three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A 2 (PLA 2 ), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A 2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome

PubMed Central

Lacro, R.V.; Dietz, H.C.; Sleeper, L.A.; Yetman, A.T.; Bradley, T.J.; Colan, S.D.; Pearson, G.D.; Tierney, E.S. Selamet; Levine, J.C.; Atz, A.M.; Benson, D.W.; Braverman, A.C.; Chen, S.; De Backer, J.; Gelb, B.D.; Grossfeld, P.D.; Klein, G.L.; Lai, W.W.; Liou, A.; Loeys, B.L.; Markham, L.W.; Olson, A.K.; Paridon, S.M.; Pemberton, V.L.; Pierpont, M.E.; Pyeritz, R.E.; Radojewski, E.; Roman, M.J.; Sharkey, A.M.; Stylianou, M.P.; Wechsler, S. Burns; Young, L.T.; Mahony, L.

2015-01-01

BACKGROUND Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (−0.139±0.013 and −0.107±0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.) PMID:25405392

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

PubMed

Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

2016-09-01

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

PubMed Central

Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

2016-01-01

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, P<0.001). The 8 week exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

PubMed

Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

2014-07-03

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

[Efficacy of coarctation resection and aortoplasty with autologous pulmonary artery patch strategy for treating coarctation of the aorta combined with hypoplastic aortic arch in infants].

PubMed

Ma, Z L; Yan, J; Li, S J; Hua, Z D; Yan, F X; Wang, X; Wang, Q

2018-03-24

Objective: To investigate the outcomes of coarctation resection and aortoplasty with autologous pulmonary artery patch for treating coarctation of the aorta combined with hypoplastic aortic arch in infants. Methods: Clinical data of 21 infants with coarctation of the aorta and hypoplastic aortic arch, who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch in Fuwai hospital from January 2009 to June 2016 were retrospectively analyzed. The age of the patients was 4 (2, 5) months,and the body weight of the patients was (5.3±1.6) kg. The patients were followed up to observe the surgery effect. Results: No perioperative death and serious complications occurred. When the patients were discharged,the systolic blood pressure of the right upper limb was lower than the preoperative systolic blood pressure ((85.7±5.9) mmHg(1 mmHg=0.133 kPa) vs. (100.7±16.6) mmHg, P< 0.001),and the systolic blood pressure of the right lower limb was higher than the preoperative systolic blood pressure ((98.7±13.3) mmHg vs. (85.6±20.8) mmHg, P< 0.001). The pressure gradient of aortic coarctation detected by echocardiography was lower than the preoperative pressure gradient ((13.1±3.8) mmHg vs. (46.2±17.1) mmHg, P< 0.001). No restenosis was detected by echocardiography at discharge. Follow-up data were obtained in 19 patients, and the follow-up time was 18 (8, 45) months.The patients grew well, and no death occurred. Restenosis occurred in 3 cases, 1 patient underwent aortic balloon dilatation and the remaining 2 patients were under follow up observation. Computed tomography angiography showed that the morphology of aortic arch was normal without signs of aortic aneurysm. Conclusion: Coarctation resection with autologous pulmonary artery patch aortoplastystrategy is considered as a safe and effective surgical method for management of infant coarctation with hypoplastic aortic arch, and this surgery method is related with satisfactory early and mid-term outcomes in this patient cohort.

3D bioprinting of biomimetic aortic vascular constructs with self-supporting cells.

PubMed

Kucukgul, Can; Ozler, S Burce; Inci, Ilyas; Karakas, Ezgi; Irmak, Ster; Gozuacik, Devrim; Taralp, Alpay; Koc, Bahattin

2015-04-01

Cardiovascular diseases are the leading cause of deaths throughout the world. Vascular diseases are mostly treated with autografts and blood vessel transplantations. However, traditional grafting methods have several problems including lack of suitable harvest sites, additional surgical costs for harvesting procedure, pain, infection, lack of donors, and even no substitutes at all. Recently, tissue engineering and regenerative medicine approaches are used to regenerate damaged or diseased tissues. Most of the tissue engineering investigations have been based on the cell seeding into scaffolds by providing a suitable environment for cell attachment, proliferation, and differentiation. Because of the challenges such as difficulties in seeding cells spatially, rejection, and inflammation of biomaterials used, the recent tissue engineering studies focus on scaffold-free techniques. In this paper, the development of novel computer aided algorithms and methods are developed for 3D bioprinting of scaffold-free biomimetic macrovascular structures. Computer model mimicking a real human aorta is generated using imaging techniques and the proposed computational algorithms. An optimized three-dimensional bioprinting path planning are developed with the proposed self-supported model. Mouse embryonic fibroblast (MEF) cell aggregates and support structures (hydrogels) are 3D bioprinted layer-by-layer according to the proposed self-supported method to form an aortic tissue construct. © 2014 Wiley Periodicals, Inc.

[Indications for and clinical outcome of the Ross procedure: a review].

PubMed

Morita, K; Kurosawa, H

2001-04-01

The Ross procedure has been used increasingly to treat aortic valve disease in children and young adults. The primary indication for the Ross procedure is to provide a permanent valve replacement in children with congenital aortic stenosis. More recently, it has been extended to young adults with a bicuspid aortic valve and small aortic annulus, especially women wishing to have children. Other possible indications include complex left ventricular outflow obstructive disease, native or prosthetic valve endocarditis, and adult aortic insufficiency with a dilated aortic annulus. Conversely, Marfan syndrome is considered to an absolute contraindication, and this procedure should be used with caution in patients with rheumatic valve disease and a dysplastic dilated aortic root because of the higher associated incidence of autograft dysfunction. The technique of total aortic root replacement has become the preferred method of autograft implantation, because it carries the lowest risk of pulmonary autograft failure. In patients with marked graft-host size mismatch, either concomitant aortic annulus reduction and fixation or aortic annulus enlargement (i.e., the Ross-Konno procedure) should be performed. The Ross Procedure International Registry data document that in the modern era (post-1986) the early and late mortality rate is 2.5% and 1%, respectively. Excellent long-term results have been reported, and the benefits of this procedure include optimal hemodynamics, low risk of endocarditis, resistance to infection in patients with active endocarditis, and nonthrombogeneicity and therefore few anticoagulation-related complications. The Ross procedure can be performed with acceptable early and mid-term mortality and excellent autograft durability. Further long-term follow-up will confirm the role of this procedure in patients with various types of aortic valve disease.

Influence of the Quantity of Aortic Valve Calcium on the Agreement Between Automated 3-Dimensional Transesophageal Echocardiography and Multidetector Row Computed Tomography for Aortic Annulus Sizing.

PubMed

Podlesnikar, Tomaz; Prihadi, Edgard A; van Rosendael, Philippe J; Vollema, E Mara; van der Kley, Frank; de Weger, Arend; Ajmone Marsan, Nina; Naji, Franjo; Fras, Zlatko; Bax, Jeroen J; Delgado, Victoria

2018-01-01

Accurate aortic annulus sizing is key for selection of appropriate transcatheter aortic valve implantation (TAVI) prosthesis size. The present study compared novel automated 3-dimensional (3D) transesophageal echocardiography (TEE) software and multidetector row computed tomography (MDCT) for aortic annulus sizing and investigated the influence of the quantity of aortic valve calcium (AVC) on the selection of TAVI prosthesis size. A total of 83 patients with severe aortic stenosis undergoing TAVI were evaluated. Maximal and minimal aortic annulus diameter, perimeter, and area were measured. AVC was assessed with computed tomography. The low and high AVC burden groups were defined according to the median AVC score. Overall, 3D TEE measurements slightly underestimated the aortic annulus dimensions as compared with MDCT (mean differences between maximum, minimum diameter, perimeter, and area: -1.7 mm, 0.5 mm, -2.7 mm, and -13 mm 2 , respectively). The agreement between 3D TEE and MDCT on aortic annulus dimensions was superior among patients with low AVC burden (<3,025 arbitrary units) compared with patients with high AVC burden (≥3,025 arbitrary units). The interobserver variability was excellent for both methods. 3D TEE and MDCT led to the same prosthesis size selection in 88%, 95%, and 81% of patients in the total population, the low, and the high AVC burden group, respectively. In conclusion, the novel automated 3D TEE imaging software allows accurate and highly reproducible measurements of the aortic annulus dimensions and shows excellent agreement with MDCT to determine the TAVI prosthesis size, particularly in patients with low AVC burden. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

[Modern aortic surgery in Marfan syndrome--2011].

PubMed

Kallenbach, K; Schwill, S; Karck, M

2011-09-01

Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.

Magnetic Resonance Measurement of Turbulent Kinetic Energy for the Estimation of Irreversible Pressure Loss in Aortic Stenosis

PubMed Central

Dyverfeldt, Petter; Hope, Michael D.; Tseng, Elaine E.; Saloner, David

2013-01-01

OBJECTIVES The authors sought to measure the turbulent kinetic energy (TKE) in the ascending aorta of patients with aortic stenosis and to assess its relationship to irreversible pressure loss. BACKGROUND Irreversible pressure loss caused by energy dissipation in post-stenotic flow is an important determinant of the hemodynamic significance of aortic stenosis. The simplified Bernoulli equation used to estimate pressure gradients often misclassifies the ventricular overload caused by aortic stenosis. The current gold standard for estimation of irreversible pressure loss is catheterization, but this method is rarely used due to its invasiveness. Post-stenotic pressure loss is largely caused by dissipation of turbulent kinetic energy into heat. Recent developments in magnetic resonance flow imaging permit noninvasive estimation of TKE. METHODS The study was approved by the local ethics review board and all subjects gave written informed consent. Three-dimensional cine magnetic resonance flow imaging was used to measure TKE in 18 subjects (4 normal volunteers, 14 patients with aortic stenosis with and without dilation). For each subject, the peak total TKE in the ascending aorta was compared with a pressure loss index. The pressure loss index was based on a previously validated theory relating pressure loss to measures obtainable by echocardiography. RESULTS The total TKE did not appear to be related to global flow patterns visualized based on magnetic resonance–measured velocity fields. The TKE was significantly higher in patients with aortic stenosis than in normal volunteers (p < 0.001). The peak total TKE in the ascending aorta was strongly correlated to index pressure loss (R2 = 0.91). CONCLUSIONS Peak total TKE in the ascending aorta correlated strongly with irreversible pressure loss estimated by a well-established method. Direct measurement of TKE by magnetic resonance flow imaging may, with further validation, be used to estimate irreversible pressure loss in aortic stenosis. PMID:23328563

Endovascular aortic repair: first twenty years.

PubMed

Koncar, Igor; Tolić, Momcilo; Ilić, Nikola; Cvetković, Slobodan; Dragas, Marko; Cinara, Ilijas; Kostić, Dusan; Davidović, Lazar

2012-01-01

Endovascular aortic/aneurysm repair (EVAR) was introduced into clinical practice at the beginning of the nineties. Its fast development had a great influence on clinicians, vascular surgeons and interventional radiologists, educational curriculums, patients, industry and medical insurance. The aim of this paper is to present the contribution of clinicians and industry to the development and advancement of endovascular aortic repair over the last 20 years. This review article presents the development of EVAR by focusing on the contribution of physicians, surgeons and interventional radiologists in the creation of the new field of vascular surgery termed hybrid vascular surgery, and also the contribution of technological advancement by a significant help of industrial representatives--engineers and their counselors. This article also analyzes studies conducted in order to compare the successfulness of EVAR with up-to-now applied open surgical repair of aortic aneurysms, and some treatment techniques of other aortic diseases. During the first two decades of its development the EVAR method was rapidly progressing and was adopted concurrently with the expansion of technology. Owing to large randomized studies, early and long-term results indicate specific complications of this method, thus influencing further technological improvement and defining risk patients groups in whom the use of the technique should be avoided. Good results are insured only in centers, specialized in vascular surgery, which have on their disposal adequate conditions for solving all complications associated with this method.

Optical pathology study of human abdominal aorta tissues using confocal micro resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Cheng-hui; Boydston-White, Susie; Wang, Wubao; Sordillo, Laura A.; Shi, Lingyan; Weisberg, Arel; Tomaselli, Vincent P.; Sordillo, Peter P.; Alfano, Robert R.

2016-03-01

Resonance Raman (RR) spectroscopic technique has a high potential for label-free and in-situ detection of biomedical lesions in vivo. This study evaluates the ability of RR spectroscopy method as an optical histopathology tool to detect the atherosclerotic plaque states of abdominal aorta in vitro. This part demonstrates the RR spectral molecular fingerprint features from different sites of the atherosclerotic abdominal aortic wall tissues. Total 57 sites of five pieces aortic samples in intimal and adventitial wall from an autopsy specimen were examined using confocal micro Raman system of WITec 300R with excitation wavelength of 532nm. The preliminary RR spectral biomarkers of molecular fingerprints indicated that typical calcified atherosclerotic plaque (RR peak at 964cm-1) tissue; fibrolipid plaque (RR peaks at 1007, 1161, 1517 and 2888cm-1) tissue, lipid pool with the fatty precipitation cholesterol) with collagen type I (RR peaks at 864, 1452, 1658, 2888 and 2948cm-1) in the soft tissue were observed and investigated.

Non-invasive imaging of flow and vascular function in disease of the aorta

PubMed Central

Whitlock, Matthew C.; Hundley, W. Gregory

2015-01-01

With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states. PMID:26381770

Application of a novel particle tracking algorithm in the flow visualization of an artificial abdominal aortic aneurysm.

PubMed

Zhang, Yang; Wang, Yuan; He, Wenbo; Yang, Bin

2014-01-01

A novel Particle Tracking Velocimetry (PTV) algorithm based on Voronoi Diagram (VD) is proposed and briefed as VD-PTV. The robustness of VD-PTV for pulsatile flow is verified through a test that includes a widely used artificial flow and a classic reference algorithm. The proposed algorithm is then applied to visualize the flow in an artificial abdominal aortic aneurysm included in a pulsatile circulation system that simulates the aortic blood flow in human body. Results show that, large particles tend to gather at the upstream boundary because of the backflow eddies that follow the pulsation. This qualitative description, together with VD-PTV, has laid a foundation for future works that demand high-level quantification.

Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome.

PubMed

Oller, Jorge; Méndez-Barbero, Nerea; Ruiz, E Josue; Villahoz, Silvia; Renard, Marjolijn; Canelas, Lizet I; Briones, Ana M; Alberca, Rut; Lozano-Vidal, Noelia; Hurlé, María A; Milewicz, Dianna; Evangelista, Arturo; Salaices, Mercedes; Nistal, J Francisco; Jiménez-Borreguero, Luis Jesús; De Backer, Julie; Campanero, Miguel R; Redondo, Juan Miguel

2017-02-01

Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology. Pharmacological inhibition of Nos2 rapidly reversed aortic dilation and medial degeneration in young Adamts1-deficient mice and in young or old MFS mice. Patients with MFS showed elevated NOS2 and decreased ADAMTS1 protein levels in the aorta. These findings uncover a possible causative role for the ADAMTS1-NOS2 axis in human TAAD and warrant evaluation of NOS2 inhibitors for therapy.

Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein.

PubMed

Jiang, Wen-Jian; Ren, Wei-Hong; Liu, Xu-Jie; Liu, Yan; Wu, Fu-Jian; Sun, Li-Zhong; Lan, Feng; Du, Jie; Zhang, Hong-Jia

2016-09-05

In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro , and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome.

4D optical coherence tomography of aortic valve dynamics in a murine mouse model ex vivo

NASA Astrophysics Data System (ADS)

Schnabel, Christian; Jannasch, Anett; Faak, Saskia; Waldow, Thomas; Koch, Edmund

2015-07-01

The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain during lifetime. Like all highly stressed materials, also these biological components undergo fatigue and signs of wear, which impinge upon cardiac output and in the end on health and living comfort of affected patients. Thereby pathophysiological changes of the aortic valve leading to calcific aortic valve stenosis (AVS) as most frequent heart valve disease in humans are of particular interest. The knowledge about changes of the dynamic behavior during the course of this disease and the possibility of early stage diagnosis could lead to the development of new treatment strategies and drug-based options of prevention or therapy. ApoE-/- mice as established model of AVS versus wildtype mice were introduced in an ex vivo artificially stimulated heart model. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behavior of the murine aortic valve and to characterize dynamic properties during artificial stimulation. OCT and high-speed video microscopy with high spatial and temporal resolution represent promising tools for the investigation of dynamic behavior and their changes in calcific aortic stenosis disease models in mice.

Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

PubMed

Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

2011-02-01

Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Comparative hemodynamics in an aorta with bicuspid and trileaflet valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2016-04-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. There are two main hypotheses to explain the increase prevalence of aortopathies in patients with BAV: the genetic and the hemodynamic. In this study, we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the curvilinear immersed boundary method coupled with an efficient thin-shell finite-element formulation for tissues to carry out fluid-structure interaction simulations of a healthy trileaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large-scale flow patterns in the ascending aorta; the shear stress magnitude, directions, and dynamics on the heart valve surfaces. The computed results are in qualitative agreement with in vivo magnetic resonance imaging data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation.

Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors.

PubMed

Lau, Eva On-Chai; Lo, Chun-Yin; Yao, Yifei; Mak, Arthur Fuk-Tat; Jiang, Liwen; Huang, Yu; Yao, Xiaoqiang

2016-01-01

Arterial baroreceptors are mechanical sensors that detect blood pressure changes. It has long been suggested that the two arterial baroreceptors, aortic and carotid baroreceptors, have different pressure sensitivities. However, there is no consensus as to which of the arterial baroreceptors are more sensitive to changes in blood pressure. In the present study, we employed independent methods to compare the pressure sensitivity of the two arterial baroreceptors. Firstly, pressure-activated action potential firing was measured by whole-cell current clamp with a high-speed pressure clamp system in primary cultured baroreceptor neurons. The results show that aortic depressor neurons possessed a higher percentage of mechano-sensitive neurons. Furthermore, aortic baroreceptor neurons show a lower pressure threshold than that of carotid baroreceptor neurons. Secondly, uniaxial stretching of baroreceptor neurons, that mimics the forces exerted on blood vessels, elicited a larger increase in intracellular Ca(2+) rise in aortic baroreceptor neurons than in carotid baroreceptor neurons. Thirdly, the pressure-induced action potential firing in the aortic depressor nerve recorded in vivo was also higher. The present study therefore provides for a basic physiological understanding on the pressure sensitivity of the two baroreceptor neurons and suggests that aortic baroreceptors have a higher pressure sensitivity than carotid baroreceptors.

Polymorphism in exon 6 of the human NT5E gene is associated with aortic valve calcification.

PubMed

Kochan, Zdzislaw; Karbowska, Joanna; Gogga, Patrycja; Kutryb-Zajac, Barbara; Slominska, Ewa M; Smolenski, Ryszard T

2016-12-01

NT5E encodes ecto-5'-nucleotidase (e5NT, CD73) which hydrolyses extracellular AMP to adenosine. Adenosine has been shown to play a protective role against aortic valve calcification (AVC). We identified two nonsynonymous missense single nucleotide polymorphisms (c.1126A > G, p.T376A and c.1136T > C, p.M379T) in exon 6 of the human NT5E gene. Since both substitutions might affect e5NT activity and consequently alter extracellular adenosine levels, we evaluated the association between NT5E alleles and calcific aortic valve disease in 119 patients (95 patients with AVC and 24 controls). In AVC patients, the frequency of the G allele at c.1126 and the frequency of the GG genotype as well as the frequency of the C allele at c.1136, and the frequencies of CC and TC genotypes tended to be higher as compared to controls. The allele and genotype frequencies in AVC patients and controls were also compared to those calculated from the 1000 Genomes Project data for control individuals of European ancestry (n = 503). We found that the frequency of the C allele at c.1136 is significantly higher in patients with AVC than in the European controls (0.111 vs. 0.054, P = 0.0052). Moreover, e5NT activity in aortic valves showed a trend toward lower levels in AVC patients with CC and TC genotypes than in those with the TT genotype. Our findings indicate that the genetic polymorphism of NT5E may contribute to the pathogenesis of calcific aortic valve disease and that the C allele of SNP c.1136 is associated with an increased risk of AVC.

Protection from cigarette smoke-induced vascular injury by recombinant human relaxin-2 (serelaxin).

PubMed

Pini, Alessandro; Boccalini, Giulia; Baccari, Maria Caterina; Becatti, Matteo; Garella, Rachele; Fiorillo, Claudia; Calosi, Laura; Bani, Daniele; Nistri, Silvia

2016-05-01

Smoking is regarded as a major risk factor for the development of cardiovascular diseases (CVD). This study investigates whether serelaxin (RLX, recombinant human relaxin-2) endowed with promising therapeutic properties in CVD, can be credited of a protective effect against cigarette smoke (CS)-induced vascular damage and dysfunction. Guinea pigs exposed daily to CS for 8 weeks were treated with vehicle or RLX, delivered by osmotic pumps at daily doses of 1 or 10 μg. Controls were non-smoking animals. Other studies were performed on primary guinea pig aortic endothelial (GPAE) cells, challenged with CS extracts (CSE) in the absence and presence of 100 ng/ml (17 nmol/l) RLX. In aortic specimens from CS-exposed guinea pigs, both the contractile and the relaxant responses to phenylephrine and acetylcholine, respectively, were significantly reduced in amplitude and delayed, in keeping with the observed adverse remodelling of the aortic wall, endothelial injury and endothelial nitric oxide synthase (eNOS) down-regulation. RLX at both doses maintained the aortic contractile and relaxant responses to a control-like pattern and counteracted aortic wall remodelling and endothelial derangement. The experiments with GPAE cells showed that CSE significantly decreased cell viability and eNOS expression and promoted apoptosis by sparkling oxygen free radical-related cytotoxicity, while RLX counterbalanced the adverse effects of CSE. These findings demonstrate that RLX is capable of counteracting CS-mediated vascular damage and dysfunction by reducing oxidative stress, thus adding a tile to the growing mosaic of the beneficial effects of RLX in CVD. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

PubMed Central

Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

2014-01-01

Objectives This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). Methods The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Results Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Conclusions Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. PMID:24533142

2D to 3D fusion of echocardiography and cardiac CT for TAVR and TAVI image guidance.

PubMed

Khalil, Azira; Faisal, Amir; Lai, Khin Wee; Ng, Siew Cheok; Liew, Yih Miin

2017-08-01

This study proposed a registration framework to fuse 2D echocardiography images of the aortic valve with preoperative cardiac CT volume. The registration facilitates the fusion of CT and echocardiography to aid the diagnosis of aortic valve diseases and provide surgical guidance during transcatheter aortic valve replacement and implantation. The image registration framework consists of two major steps: temporal synchronization and spatial registration. Temporal synchronization allows time stamping of echocardiography time series data to identify frames that are at similar cardiac phase as the CT volume. Spatial registration is an intensity-based normalized mutual information method applied with pattern search optimization algorithm to produce an interpolated cardiac CT image that matches the echocardiography image. Our proposed registration method has been applied on the short-axis "Mercedes Benz" sign view of the aortic valve and long-axis parasternal view of echocardiography images from ten patients. The accuracy of our fully automated registration method was 0.81 ± 0.08 and 1.30 ± 0.13 mm in terms of Dice coefficient and Hausdorff distance for short-axis aortic valve view registration, whereas for long-axis parasternal view registration it was 0.79 ± 0.02 and 1.19 ± 0.11 mm, respectively. This accuracy is comparable to gold standard manual registration by expert. There was no significant difference in aortic annulus diameter measurement between the automatically and manually registered CT images. Without the use of optical tracking, we have shown the applicability of this technique for effective fusion of echocardiography with preoperative CT volume to potentially facilitate catheter-based surgery.

The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease.

PubMed

Adenwalla, Sherna F; Graham-Brown, Matthew P M; Leone, Francesca M T; Burton, James O; McCann, Gerry P

2017-08-01

Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy

PubMed Central

Lacro, Ronald V.; Guey, Lin T.; Dietz, Harry C.; Pearson, Gail D.; Yetman, Anji T.; Gelb, Bruce D.; Loeys, Bart L.; Benson, D. Woodrow; Bradley, Timothy J.; De Backer, Julie; Forbus, Geoffrey A.; Klein, Gloria L.; Lai, Wyman W.; Levine, Jami C.; Lewin, Mark B.; Markham, Larry W.; Paridon, Stephen M.; Pierpont, Mary Ella; Radojewski, Elizabeth; Selamet Tierney, Elif Seda; Sharkey, Angela M.; Wechsler, Stephanie Burns; Mahony, Lynn

2013-01-01

Background The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. Methods and results Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area–adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. Conclusions Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome. PMID:23622922

Effect of load alterations on the effective regurgitant orifice area in chronic aortic regurgitation.

PubMed

Kim, Y J; Jones, M; Shiota, T; Tsujino, H; Qin, J X; Bauer, F; Sitges, M; Kwan, J; Cardon, L A; Zetts, A D; Thomas, J D

2002-10-01

To evaluate the load dependence of effective regurgitant orifice area (ROA) in an animal model of chronic aortic regurgitation. Eight sheep were studied 10-20 weeks after the surgical creation of aortic regurgitation. After baseline studies, 500 ml of blood, angiotensin II, and nitroprusside were infused sequentially. Electromagnetic flow meters were used as reference standards to determine aortic regurgitation volume. The time-velocity integral was acquired using the continuous wave Doppler method. Baseline aortic regurgitant volume varied from 8 ml (regurgitant fraction 28%) to 29 ml (59%), with a mean (SD) value of 17 (8) ml; mean ROA was 0.15 (0.05) cm2. During angiotensin II infusion, aortic regurgitation volume (20 (8) ml) and mean diastolic aortoventricular pressure gradient (62 (18) mm Hg) increased by 26 (16)% and 48 (64)%, respectively (p < 0.01 for both). ROA did not change (0.16 (0.06) cm(2), p = 0.15). During nitroprusside infusion, aortic regurgitant volume (13 (7) ml, p = 0.05) and diastolic pressure gradient (25 (13) mm Hg, p < 0.05) decreased. ROA did not change (0.15 (0.05) cm2). When analysing 32 stages together, aortic regurgitant volume (r = 0.78, p < 0.01) and regurgitant fraction (r = 0.55, p < 0.01) correlated well with ROA. However, diastolic pressure gradient (r = 0.28) was not significantly correlated with ROA. In an animal model of chronic aortic regurgitation, ROA did not change with load alterations.

Longitudinal and Circumferential Strain of the Proximal Aorta

PubMed Central

Bell, Vanessa; Mitchell, William A.; Sigurðsson, Sigurður; Westenberg, Jos J. M.; Gotal, John D.; Torjesen, Alyssa A.; Aspelund, Thor; Launer, Lenore J.; de Roos, Albert; Gudnason, Vilmundur; Harris, Tamara B.; Mitchell, Gary F.

2014-01-01

Background Accurate assessment of mechanical properties of the proximal aorta is a requisite first step for elucidating the pathophysiology of isolated systolic hypertension. During systole, substantial proximal aortic axial displacement produces longitudinal strain, which we hypothesize causes variable underestimation of ascending aortic circumferential strain compared to values in the longitudinally constrained descending aorta. Methods and Results To assess effects of longitudinal strain, we performed magnetic resonance imaging in 375 participants (72 to 94 years old, 204 women) in the Age, Gene/Environment Susceptibility‐Reykjavik Study and measured aortic circumferential and longitudinal strain. Circumferential ascending aortic area strain uncorrected for longitudinal strain was comparable in women and men (mean [95% CI], 8.3 [7.8, 8.9] versus 7.9 [7.4, 8.5]%, respectively, P=0.3). However, longitudinal strain was greater in women (8.5±2.5 versus 7.0±2.5%, P<0.001), resulting in greater longitudinally corrected circumferential ascending aortic strain (14.4 [13.6, 15.2] versus 13.0 [12.4, 13.7]%, P=0.010). Observed circumferential descending aortic strain, which did not require correction (women: 14.0 [13.2, 14.8], men: 12.4 [11.6, 13.2]%, P=0.005), was larger than uncorrected (P<0.001), but comparable to longitudinally corrected (P=0.12) circumferential ascending aortic strain. Carotid‐femoral pulse wave velocity did not correlate with uncorrected ascending aortic strain (R=−0.04, P=0.5), but was inversely related to longitudinally corrected ascending and observed descending aortic strain (R=−0.15, P=0.004; R=−0.36, P<0.001, respectively). Longitudinal strain was also inversely related to carotid‐femoral pulse wave velocity and other risk factors for higher aortic stiffness including treated hypertension. Conclusions Longitudinal strain creates substantial and variable errors in circumferential ascending aortic area strain measurements, particularly in women, and should be considered to avoid misclassification of ascending aortic stiffness. PMID:25523153

Relation of the aortic stiffness with the GRACE risk score in patients with the non ST-segment elevation myocardial infarction

PubMed Central

Omer, Gedikli; Gokhan, Aksan; Adem, Uzun; Sabri, Demircan; Korhan, Soylu

2014-01-01

Background: Current guidelines recommend clinical risk scoring systems for the patients diagnosed and determinated treatment strategy with in Non-ST-elevation elevation myocardial infarction (NSTEMI). Previous studies demonstrated association between aortic elasticity properties, stiffness and severity CAD. However, the associations between Aortic stiffness, elasticity properties and clinical risk scores have not been investigated. In the present study we have evaluated the relation between the Global Registry of Acute Coronary Events (GRACE) risk score and aortic stiffness in patients with NSTEMI. Method: We prospectively analyzed 87 consecutive patients with NSTEMI. Aortic elastic parameter and stiffness parameter were calculated from the echocardiographically derived thoracic aortic diameters (mm/m2), and the measurement of pulse pressure obtained by cuff sphygmomanometry. We have categorized the patients in to two groups as low ((n = 45) (GRACE risk score ≤ 140)) and high ((n = 42) (GRACE risk score > 140)) risk group according to GRACE risk score and compare the both groups. Results: Table 1 shows baseline characteristics of patients. Our study showed that Aortic strain was significantly low (3.5 ± 1.4, 7.9 ± 2.3 respectively, p < 0.001) and aortic stiffness index was significantly high (3.9 ± 0.38; 3 ± 0.35, respectively, p < 0.001) in the high risk group values compared to those with low risk group. The aortic stiffness index was the only independent predictor of GRACE risk score (OR: 119.390; 95% CI: 2.925-4872.8; p = 0.011) in multivariate analysis. Conclusion: We found a significant correlation between aortic stiffness, impaired elasticity and GRACE risk score. Aortic stiffness index was the only independent variable of the high GRACE risk score. The inclusion of aortic stiffness into the GRACE risk score could allow improved risk classification of patients with ACS at admission and this may be important in the diagnosis, follow up and treatment of the patients. PMID:25356178

Genetic Bases of Bicuspid Aortic Valve: The Contribution of Traditional and High-Throughput Sequencing Approaches on Research and Diagnosis

PubMed Central

Giusti, Betti; Sticchi, Elena; De Cario, Rosina; Magi, Alberto; Nistri, Stefano; Pepe, Guglielmina

2017-01-01

Bicuspid aortic valve (BAV) is a common (0.5–2.0% of general population) congenital heart defect with increased prevalence of aortic dilatation and dissection. BAV has an autosomal dominant inheritance with reduced penetrance and variable expressivity. BAV has been described as an isolated trait or associated with syndromic conditions [e.g., Marfan Marfan syndrome or Loeys-Dietz syndrome (MFS, LDS)]. Identification of a syndromic condition in a BAV patient is clinically relevant to personalize aortic surgery indication. A 4-fold increase in BAV prevalence in a large cohort of unrelated MFS patients with respect to general population was reported, as well as in LDS patients (8-fold). It is also known that BAV is more frequent in patients with thoracic aortic aneurysm (TAA) related to mutations in ACTA2, FBN1, and TGFBR2 genes. Moreover, in 8 patients with BAV and thoracic aortic dilation, not fulfilling the clinical criteria for MFS, FBN1 mutations in 2/8 patients were identified suggesting that FBN1 or other genes involved in syndromic conditions correlated to aortopathy could be involved in BAV. Beyond loci associated to syndromic disorders, studies in humans and animal models evidenced/suggested the role of further genes in non-syndromic BAV. The transcriptional regulator NOTCH1 has been associated with the development and acceleration of calcium deposition. Genome wide marker-based linkage analysis demonstrated a linkage of BAV to loci on chromosomes 18, 5, and 13q. Recently, a role for GATA4/5 in aortic valve morphogenesis and endocardial cell differentiation has been reported. BAV has also been associated with a reduced UFD1L gene expression or involvement of a locus containing AXIN1/PDIA2. Much remains to be understood about the genetics of BAV. In the last years, high-throughput sequencing technologies, allowing the analysis of large number of genes or entire exomes or genomes, progressively became available. The latter issue together with the development of “BigData” analysis methods improving their interpretation and integration with clinical data represents a promising opportunity to increase the disease knowledge and diagnosis in monogenic and multifactorial complex traits. This review summarized the main knowledge on the BAV genetic bases, the role of genetic diagnosis in BAV patient managements and the crucial challenges for the comprehension of genetics of BAV in research and diagnosis. PMID:28883797

Novel three-sinus enlargement technique for supravalvular aortic stenosis without aortic transection.

PubMed

Yokoyama, Shinya; Nagato, Hisao; Yoshida, Yuichi; Nagasaka, Shigeo; Kaneda, Kozo; Nishiwaki, Noboru

2016-01-16

Although repair of a supravalvular aortic stenosis (SVAS) can be performed with low mortality rates, surgery for the complex form of SVAS continues to be associated with a high incidence of residual stenosis. The patient was referred to our hospital at 1 month of age and was diagnosed with aortic valve stenosis (AS) by using echocardiography. Cardiac catheterization revealed moderate AS, and subsequent left ventriculography revealed discrete stenosis of the sino-tubular junction and a narrowed proximal ascending aorta. We performed a reconstructive operation for such heart defects involving novel three-sinus and ascending aorta enlargement without aortic root transection in a 6-month-old boy. Our novel three-sinus enlargement technique is suitable for treating each type of SVAS and is a useful method for a baby particularly less than 10 kg without disturbing the growth of the ascending aorta.

Modeling of the aorta artery aneurysms and renal artery stenosis using cardiovascular electronic system

PubMed Central

Hassani, Kamran; Navidbakhsh, Mahdi; Rostami, Mostafa

2007-01-01

Background The aortic aneurysm is a dilatation of the aortic wall which occurs in the saccular and fusiform types. The aortic aneurysms can rupture, if left untreated. The renal stenosis occurs when the flow of blood from the arteries leading to the kidneys is constricted by atherosclerotic plaque. This narrowing may lead to the renal failure. Previous works have shown that, modelling is a useful tool for understanding of cardiovascular system functioning and pathophysiology of the system. The present study is concerned with the modelling of aortic aneurysms and renal artery stenosis using the cardiovascular electronic system. Methods The geometrical models of the aortic aneurysms and renal artery stenosis, with different rates, were constructed based on the original anatomical data. The pressure drop of each section due to the aneurysms or stenosis was computed by means of computational fluid dynamics method. The compliance of each section with the aneurysms or stenosis is also calculated using the mathematical method. An electrical system representing the cardiovascular circulation was used to study the effects of these pressure drops and the compliance variations on this system. Results The results showed the decreasing of pressure along the aorta and renal arteries lengths, due to the aneurysms and stenosis, at the peak systole. The mathematical method demonstrated that compliances of the aorta sections and renal increased with the expansion rate of the aneurysms and stenosis. The results of the modelling, such as electrical pressure graphs, exhibited the features of the pathologies such as hypertension and were compared with the relevant experimental data. Conclusion We conclude from the study that the aortic aneurysms as well as renal artery stenosis may be the most important determinant of the arteries rupture and failure. Furthermore, these pathologies play important rules in increase of the cardiovascular pulse pressure which leads to the hypertension. PMID:17559685

Accuracy and reproducibility of novel echocardiographic three-dimensional automated software for the assessment of the aortic root in candidates for thanscatheter aortic valve replacement.

PubMed

García-Martín, Ana; Lázaro-Rivera, Carla; Fernández-Golfín, Covadonga; Salido-Tahoces, Luisa; Moya-Mur, Jose-Luis; Jiménez-Nacher, Jose-Julio; Casas-Rojo, Eduardo; Aquila, Iolanda; González-Gómez, Ariana; Hernández-Antolín, Rosana; Zamorano, José Luis

2016-07-01

A specialized three-dimensional transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced; the system automatically configures a geometric model of the aortic root from the images obtained by 3D-TOE and performs quantitative analysis of these structures. The aim of this study was to compare the measurements of the aortic annulus (AA) obtained by the new model to that obtained by 3D-TOE and multidetector computed tomography (MDCT) in candidates to transcatheter aortic valve implantation (TAVI) and to assess the reproducibility of this new method. We included 31 patients who underwent TAVI. The AA diameters and area were evaluated by the manual 3D-TOE method and by the automatic software. We showed an excellent correlation between the measurements obtained by both methods: intra-class correlation coefficient (ICC): 0.731 (0.508-0.862), r: 0.742 for AA diameter and ICC: 0.723 (0.662-0.923), r: 0.723 for the AA area, with no significant differences regardless of the method used. The interobserver variability was superior for the automatic measurements than for the manual ones. In a subgroup of 10 patients, we also found an excellent correlation between the automatic measurements and those obtained by MDCT, ICC: 0.941 (0.761-0.985), r: 0.901 for AA diameter and ICC: 0.853 (0.409-0.964), r: 0.744 for the AA area. The new automatic 3D-TOE software allows modelling and quantifying the aortic root from 3D-TOE data with high reproducibility. There is good correlation between the automated measurements and other 3D validated techniques. Our results support its use in clinical practice as an alternative to MDCT previous to TAVI. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Extracting a Purely Non-rigid Deformation Field of a Single Structure

NASA Astrophysics Data System (ADS)

Demirci, Stefanie; Manstad-Hulaas, Frode; Navab, Nassir

During endovascular aortic repair (EVAR) treatment, the aortic shape is subject to severe deformation that is imposed by medical instruments such as guide wires, catheters, and the stent graft. The problem definition of deformable registration of images covering the entire abdominal region, however, is highly ill-posed. We present a new method for extracting the deformation of an aneurysmatic aorta. The outline of the procedure includes initial rigid alignment of two abdominal scans, segmentation of abdominal vessel trees, and automatic reduction of their centerline structures to one specified region of interest around the aorta. Our non-rigid registration procedure then only computes local non-rigid deformation and leaves out all remaining global rigid transformations. In order to evaluate our method, experiments for the extraction of aortic deformation fields are conducted on 15 patient datasets from endovascular aortic repair (EVAR) treatment. A visual assessment of the registration results were performed by two vascular surgeons and one interventional radiologist who are all experts in EVAR procedures.

In vitro study on the effects of some selected agonists and antagonists of alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed aortic smooth muscle in humans.

PubMed

Gnus, J; Czerski, A; Ferenc, S; Zawadzki, W; Witkiewicz, W; Hauzer, W; Rusiecka, A; Bujok, J

2012-02-01

The study included 18 sections of the aneurysmally-changed abdominal aortas, obtained from patients of the Provincial Specialist Hospital in Wroclaw and 18 sections of normal abdominal aortas obtained from swine. The collected samples were placed horizontally in the incubation chamber. Changes in their transverse section area were registered. They were stretched to a tension of 5 mN. Krebs-Henseleit buffer was used as the incubatory environment. Incubation of the sections was performed at a temperature of 37°C, in the gaseous mixture of oxygen and carbon dioxide used in the following proportion: 95% of O(2) and 5% of CO(2). Contractions of the aorta were registered with isotonic transducers (Letica Scientific Instruments). In the studies, we examined the influence of α(1)-adrenergic receptors (and their subtypes α(1A), α(1B), α(1D)) on the contractility of the aortic muscle in humans and swine by their stimulation or inhibition with some selected agonists or antagonists. This time, it was shown that the stimulation of α(1)-adrenergic receptors leads to contractions of the human and swine aortic muscle; the observed increase in the muscle tone may follow from the stimulation of all subtypes of alpha-1 receptor (α(1A), α(1B), α(1D)). All three subtypes of 1-adrenergic receptor are engaged in vasoconstriction, especially of α(1A) and α(1D) subtypes; the α(1B) subtype is less significant for aortic contractility. The contractile response of the aneurysmally-changed abdominal aorta in humans to agonists of α-adrenergic receptors was significantly less intense than that of the normal porcine aorta. It can be concluded that aneurysms influence the contractile response of the aorta.

Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

PubMed Central

2012-01-01

Background Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735 PMID:22839417

Assessment of mitral regurgitation in dogs: comparison of results of echocardiography with magnetic resonance imaging.

PubMed

Sargent, J; Connolly, D J; Watts, V; Mõtsküla, P; Volk, H A; Lamb, C R; Fuentes, V Luis

2015-11-01

Echocardiography is used routinely to assess mitral regurgitation severity, but echocardiographic measures of mitral regurgitation in dogs have not been compared with other quantitative methods. The study aim was to compare echocardiographic measures of mitral regurgitation with cardiac magnetic resonance imaging-derived mitral regurgitant fraction in small-breed dogs. Dogs with myxomatous mitral valve disease scheduled for magnetic resonance imaging assessment of neurological disease were recruited. Correlations were tested between cardiac magnetic resonance imaging-derived mitral regurgitant fraction and the following echocardiographic measures: vena contracta/aortic diameter, transmitral E-wave velocity, amplitude of mitral prolapse/aortic diameter, diastolic left ventricular diameter:aortic diameter, left atrium:aortic diameter, mitral regurgitation jet area ratio and regurgitant fraction calculated using the proximal isovelocity surface area method. Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction was attempted in 21 dogs. Twelve consecutive, complete studies were obtained and 10 dogs were included in the final analysis: vena contracta/aortic diameter (r = 0 · 89, p = 0 · 001) and E-wave velocity (r = 0 · 86, p = 0 · 001) had the strongest correlations with cardiac magnetic resonance imaging-derived mitral regurgitant fraction. E velocity had superior repeatability and could be measured in all dogs. The presence of multiple jets precluded vena contracta/aortic diameter measurement in one dog. Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction is feasible but technically demanding. The echocardiographic measures that correlated most closely with cardiac magnetic resonance imaging-derived mitral regurgitant fraction were vena contracta/aortic diameter and E-wave velocity. © 2015 British Small Animal Veterinary Association.

Obtaining the biomechanical behavior of ascending aortic aneurysm via the use of novel speckle tracking echocardiography.

PubMed

Alreshidan, Mohammed; Shahmansouri, Nastaran; Chung, Jennifer; Lash, Vynka; Emmott, Alexander; Leask, Richard L; Lachapelle, Kevin

2017-04-01

Ex vivo measurement of ascending aortic biomechanical properties may help understand the risk for rupture or dissection of dilated ascending aortas. A validated in vivo method that can predict aortic biomechanics does not exist. Speckle tracking transesophageal echocardiography (TEE) has been used to measure ventricular stiffness; we sought to determine whether speckle TEE could be adapted to estimate aortic stiffness in vivo and compare these findings with those obtained by ex vivo tissue measurements. A total of 17 patients undergoing ascending aortic resection were recruited to with a mean aortic diameter was 56.16 ± 15 mm. Intraoperative speckle TEE tracking analysis was used to calculate aortic stiffness index using the following equation: β2=ln(SBP/DBP)/AoS, where β2 is the stiffness index; SBP is systolic blood pressure; DBP is diastolic blood pressure; and AoS is the circumferential strain. Ex vivo stiffness was obtained by mechanical tissue testing according to previously described methods. The aortic ring at the pulmonary trunk was divided into 4 equal quadrants. The in vivo stiffness index for the inner curvature, anterior wall, outer curvature, and posterior wall were 0.0544 ± 0.0490, 0.0295 ± 0.0199, 0.0411 ± 0.0328, and 0.0502 ± 0.0320, respectively. The mean ex vivo 25% apparent stiffness for inner curvature, anterior wall, outer curvature, and posterior wall were 0.0616 ± 0.0758 MPa, 0.0352 ± 0.00992 MPa, 0.0405 ± 0.0199 MPa, and 0.0327 ± 0.0106 MPa, respectively. The patient-matched ex vivo 25% apparent stiffness and in vivo stiffness index were not significantly different (P = .8617, 2-way analysis of variance with repeated measures). The use of speckle TEE appears to be a promising technique to estimate ex vivo mechanical properties of the ascending aortic tissue. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

Fatal Saccharomyces cerevisiae aortic graft infection.

PubMed

Smith, Davey; Metzgar, David; Wills, Christopher; Fierer, Joshua

2002-07-01

Saccharomyces cerevisiae is a yeast commonly used in baking and a frequent colonizer of human mucosal surfaces. It is considered relatively nonpathogenic in immunocompetent adults (J. N. Aucott, J. Fayan, H. Grossnicklas, A. Morrissey, M. M. Lederman, and R. A. Salata, Rev. Infect. Dis. 12:406-411, 1990). We present a case of S. cerevisiae fungemia and aortic graft infection in an immunocompetent adult. This is the first reported case of S. cerevisiae fungemia where the identity of the pathogen was confirmed by rRNA sequencing.

First-in-human implantation of a novel transfemoral selfexpanding transcatheter heart valve to treat pure aortic regurgitation.

PubMed

Schäfer, Ulrich; Schirmer, Johannes; Niklas, Schofer; Harmel, Eva; Deuschl, Florian; Conradi, Lenard

2017-12-20

Here we will describe the first case of a novel JenaValve design (JenaValve Technology, Irvine, CA, USA) using the transfemoral approach in a 78-year-old female patient with pure aortic regurgitation. The implantation was successfully performed with good haemodynamics and good clinical outcome at six-month follow- up. The technology is especially appealing in non-calcified anatomies due to the clipping mechanism which was previously utilised in the transapical design.

Identification of EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies

PubMed Central

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-01-01

We performed an exome-wide association study (EWAS) to identify genetic variants - in particular, low-frequency or rare variants with a moderate to large effect size - that confer susceptibility to aortic aneurysm with 8,782 Japanese subjects (456 patients with aortic aneurysm, 8,326 control individuals) and with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The correlation of allele frequencies for 41,432 single nucleotide polymorphisms (SNPs) that passed quality control to aortic aneurysm was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21×10−6 was considered statistically significant. The EWAS revealed 59 SNPs that were significantly associated with aortic aneurysm. None of these SNPs was significantly (P<2.12×10−4) associated with aortic aneurysm by multivariable logistic regression analysis with adjustment for age, gender and hypertension, although 8 SNPs were related (P<0.05) to this condition. Examination of the correlation of these latter 8 SNPs to true or dissecting aortic aneurysm separately showed that rs1465567 [T/C (W229R)] of the EGF-like, fibronectin type III, and laminin G domains gene (EGFLAM) (dominant model; P=0.0014; odds ratio, 1.63) was significantly (P<0.0016) associated with true aortic aneurysm. We next performed EWASs for true or dissecting aortic aneurysm separately and found that 45 and 19 SNPs were significantly associated with these conditions, respectively. Multivariable logistic regression analysis with adjustment for covariates revealed that rs113710653 [C/T (E231K)] of the spermatogenesis- and centriole associated 1-like gene (SPATC1L) (dominant model; P=0.0002; odds ratio, 5.32) and rs143881017 [C/T (R140H)] of the ribonuclease A family member 13 gene (RNASE13) (dominant model; P=0.0006; odds ratio, 5.77) were significantly (P<2.78×10−4 or P<6.58×10−4, respectively) associated with true or dissecting aortic aneurysm, respectively. EGFLAM and SPATC1L may thus be susceptibility loci for true aortic aneurysm and RNASE13 may be such a locus for dissecting aneurysm in Japanese individuals. PMID:28339009

Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function

PubMed Central

Touat-Hamici, Zahia; Weidmann, Henri; Blum, Yuna; Proust, Carole; Durand, Hervé; Iannacci, Francesca; Codoni, Veronica; Gaignard, Pauline; Thérond, Patrice; Civelek, Mete; Karabina, Sonia A.; Lusis, Aldons J.; Cambien, François; Ninio, Ewa

2016-01-01

Aims Lipid phosphate phosphatase 3; type 2 phosphatidic acid phosphatase β (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby terminating signalling of lipid substrates including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is associated with coronary artery disease, which prompted us to investigate the possible role of LPP3 in human endothelial dysfunction, a condition promoting atherosclerosis. Methods and results To study the role of LPP3 in endothelial cells we used human primary aortic endothelial cells (HAECs) in which LPP3 was silenced or overexpressed using either wild type or mutated cDNA constructs. LPP3 silencing in HAECs enhanced secretion of inflammatory cytokines, leucocyte adhesion, cell survival, and migration and impaired angiogenesis, whereas wild-type LPP3 overexpression reversed these effects and induced apoptosis. We also demonstrated that LPP3 expression was negatively correlated with vascular endothelial growth factor expression. Mutations in either the catalytic or the arginine-glycine-aspartate (RGD) domains impaired endothelial cell function and pharmacological inhibition of S1P or LPA restored it. LPA was not secreted in HAECs under silencing or overexpressing LPP3. However, the intra- and extra-cellular levels of S1P tended to be correlated with LPP3 expression, indicating that S1P is probably degraded by LPP3. Conclusions We demonstrated that LPP3 is a negative regulator of inflammatory cytokines, leucocyte adhesion, cell survival, and migration in HAECs, suggesting a protective role of LPP3 against endothelial dysfunction in humans. Both the catalytic and the RGD functional domains were involved and S1P, but not LPA, might be the endogenous substrate of LPP3. PMID:27694435

Spectrum of Abdominal Aortic Disease in a Tertiary Health Care Setup: MDCT Based Observational Study

PubMed Central

Kumar, DG Santosh; Gadabanahalli, Karthik; Kalyanpur, Arjun

2016-01-01

Introduction Abdominal aortic disease is an important cause of clinical disability that requires early detection by imaging methods for prompt and effective management. Understanding regional disease pattern and prevalence has a bearing on healthcare management and resource planning. Non-invasive, conclusive imaging strategy plays an important role in the detection of disease. Multi-Detector Computed Tomography (MDCT) with its technological developments provides affordable, accurate and comprehensive imaging solution. Aim To evaluate regional demography of abdominal aortic disease spectrum detected using MDCT imaging data in a tertiary hospital. Materials and Methods A descriptive study was conducted based on MDCT imaging data of patients who were investigated with clinical diagnosis of abdominal aortic disease, from March 2008-2010, over a period of 24 months. Patients were examined with the contrast-enhanced MDCT examination. Morphological diagnosis of the aortic disease was based on changes in relative aortic caliber, luminal irregularity, presence of wall calcification, dissection or thrombus and evidence of major branch occlusion. Patients were categorized into four groups based on imaging findings. MDCT information and associated clinical parameters were examined and correlated to management of patient. Descriptive statistical data, namely mean, standard deviation and frequency of disease were evaluated. Results A total of 90 out of 210 patients (43%) were detected with the abdominal aortic abnormality defined by imaging criteria. Group I, comprising of patients with atherosclerosis –including those with complications, constituted 65.5% of the patients. Group II represented patients with aneurysms (45.5%). Group III, consisting of 32.2% of the patients, contained those with dissections. The rest of the patients, including patients with aorto-arteritis, were classified as group IV. Eight patients with aneurysm and one patient with aorto-arteritis were considered for surgical treatment. Ten patients with dissection underwent endovascular procedure. Rest of the patients was managed conservatively. Conclusion Aortic disease was observed in 43% of investigated patients. Atherosclerosis with and without aortic aneurysm constituted the largest group. MDCT provided comprehensive information about the lesion and associated complications. In view of the wider availability and desired imaging qualities, MDCT provided optimal information for diagnosis and management of aortic pathology. Majority of our patients (90%) were treated conservatively. PMID:28050476

Aortic stiffness increases in proportion to the severity of apnoea-hypopnea index in patients with obstructive sleep apnoea syndrome.

PubMed

Çörtük, Mustafa; Akyol, Selahattin; Baykan, Ahmet O; Kiraz, Kemal; Uçar, Hakan; Çaylı, Murat; Kandiş, Hayati

2016-07-01

Obstructive sleep apnoea syndrome (OSA) and aortic stiffness are associated with an increased risk of cardiovascular morbidity and mortality. Although aortic stiffness increased in patients with OSA, the relationship between severity of OSA indicated with apnoea-hypopnea index (AHI) and aortic stiffness was not investigated in previous studies. The aim of this study is to investigate the relationship between the severity of OSA and aortic stiffness. In the present study, 90 consecutive OSA patients definite diagnosed with sleep test were prospectively included (mean age 54.5 ± 11.6 years). Aortic pulse wave velocity (PWV) and augmentation index (AIx) were calculated using the single-point method via the Mobil-O-Graph® ARCsolver algorithm. Aortic distensibility (AD) was calculated from the echocardiographically derived ascending aorta diameters and haemodynamic pressure measurements. Overnight full-laboratory polysomnography examination was conducted on each subject. Patients were classified into two groups according to their median AHI values (AHIlow and AHIhigh groups). PWV values were higher and AD values were lower in AHIhigh group compared with AHIlow group (P < 0.05, for all). AHI was associated with body mass index (BMI), systolic blood pressure, pulse pressure, aortic diameter, AD, AIx and PWV in bivariate analysis (P < 0.05, for all). Multivariate linear regression analysis showed that AHI was independently associated with BMI (β = 0.175, P = 0.047), PWV (β = 0.521, P < 0.001) and aortic distensibility (β = -0.223, P = 0.020). Aortic stiffness is associated both with the presence and the severity of OSA. © 2014 John Wiley & Sons Ltd.

Type of Valvular Heart Disease Requiring Surgery in the 21st Century: Mortality and Length-of-Stay Related to Surgery

PubMed Central

Boudoulas, Konstantinos Dean; Ravi, Yazhini; Garcia, Daniel; Saini, Uksha; Sofowora, Gbemiga G.; Gumina, Richard J.; Sai-Sudhakar, Chittoor B.

2013-01-01

Aim: While the incidence of rheumatic heart disease has declined dramatically over the last half-century, the number of valve surgeries has not changed. This study was undertaken to define the most common type of valvular heart disease requiring surgery today, and determine in-hospital surgical mortality and length-of-stay (LOS) for isolated aortic or mitral valve surgery in a United States tertiary-care hospital. Methods: Patients with valve surgery between January 2002 to June 2008 at The Ohio State University Medical Center were studied. Patients only with isolated aortic or mitral valve surgery were analyzed. Results: From 915 patients undergoing at least aortic or mitral valve surgery, the majority had concomitant cardiac proce-dures mostly coronary artery bypass grafting (CABG); only 340 patients had isolated aortic (n=204) or mitral (n=136) valve surgery. In-hospital surgical mortality for mitral regurgitation (n=119), aortic stenosis (n=151), aortic insufficiency (n=53) and mitral stenosis (n=17) was 2.5% (replacement 3.4%; repair 1.6%), 3.9%, 5.6% and 5.8%, respectively (p=NS). Median LOS for aortic insufficiency, aortic stenosis, mitral regurgitation, and mitral stenosis was 7, 8, 9 (replacement 11.5; repair 7) and 11 days, respectively (p<0.05 for group). In-hospital surgical mortality for single valve surgery plus CABG was 10.2% (p<0.005 compared to single valve surgery). Conclusions: Aortic stenosis and mitral regurgitation are the most common valvular lesions requiring surgery today. Surgery for isolated aortic or mitral valve disease has low in-hospital mortality with modest LOS. Concomitant CABG with valve surgery increases mortality substantially. Hospital analysis is needed to monitor quality and stimulate improvement among Institutions. PMID:24339838

New predictor of aortic enlargement in uncomplicated type B aortic dissection based on elliptic Fourier analysis.

PubMed

Sato, Hiroshi; Ito, Toshiro; Kuroda, Yosuke; Uchiyama, Hiroki; Watanabe, Toshitaka; Yasuda, Naomi; Nakazawa, Junji; Harada, Ryo; Kawaharada, Nobuyoshi

2017-12-01

This study aimed to re-examine the conventional predictive factors for dissected aortic enlargement, such as the aortic and false lumen diameter and to consider whether the morphological elements of the dissected aorta could be predictors by quantifying the 'shape' of the true lumen based on elliptic Fourier analysis. A total of 80 patients with uncomplicated type B aortic dissection were included. The patients were divided into 'Enlargement group' and 'No Change group.' Between the 2 groups, the mean systolic blood pressure during follow-up, aortic and false lumen maximum diameters, and analysed morphological data were compared using each statistical method. The maximum aortic and false lumen diameters were significantly larger in the Enlargement group than in the No Change group (39.3 vs 35.9 mm; P = 0.0058) (23.5 vs 18.2 mm; P = 0.000095). The principal component 1, which is the data calculated by elliptic Fourier analysis, was significantly lower in the Enlargement group than in the No Change group (0.020 vs - 0.072; P = 0.000049). The mean systolic blood pressure ≥130 mmHg, aortic diameter, false lumen diameter and principal component 1 were included in the Cox proportional hazard model as covariates to determine the significant predictive variable. Principal component 1 demonstrated the only significance with aortic enlargement on multivariate analysis (odds ratio = 0.32; P = 0.048). The analysed and calculated morphological data of the shape of the true lumen can be more effective predictive factors of aortic enlargement of type B dissection than the conventional factors. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

PubMed Central

Fedorova, Olga V.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; Fleenor, Bradley S.; Lakatta, Edward G.; Bagrov, Alexei Y.; Seals, Douglas R.

2013-01-01

Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77±9 mmol/d) and 5 weeks of a normal-sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-sodium condition (all P<0.05). Across all weeks, marinobufagenin excretion was related with systolic BP (slope=0.61, P<0.001) and sodium excretion (slope=0.46, P<0.001). These associations persisted during the normal- but not the low-sodium condition (both P<0.005). Marinobufagenin excretion also was associated with aortic pulse-wave velocity (slope=0.70, P=0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P=0.006). Conclusions These results show, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets. PMID:23929930

Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage.

PubMed

White, Joseph M; Cannon, Jeremy W; Stannard, Adam; Burkhardt, Gabriel E; Spencer, Jerry R; Williams, Ken; Oh, John S; Rasmussen, Todd E

2011-11-01

The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 μg and 43.5 μg vs. 12.4 μg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted.

EXPRESSION OF NeuGc ON PIG CORNEAS AND ITS POTENTIAL SIGNIFICANCE IN PIG CORNEAL XENOTRANSPLANTATION

PubMed Central

Lee, Whayoung; Miyagawa, Yuko; Long, Cassandra; Ekser, Burcin; Walters, Eric; Ramsoondar, Jagdeece; Ayares, David; Tector, A. Joseph; Cooper, David K. C.; Hara, Hidetaka

2016-01-01

Purpose Pigs expressing neither galactose-α1,3-galactose (Gal) nor N-glycolylneuraminic acid (NeuGc) take xenotransplantation one step closer to the clinic. Our aims were (i) to document the lack of NeuGc expression on corneas and aortas, and cultured endothelial cells (aortic [AECs]; corneal [CECs]) of GTKO/NeuGcKO pigs, and (ii) to investigate whether the absence of NeuGc reduced human antibody binding to the tissues and cells. Methods Wild-type (WT), GTKO, and GTKO/NeuGcKO pig were used for the study. Human tissues and cultured cells were negative controls. Immunofluorescence staining was performed using anti-Gal and anti-NeuGc antibodies, and to determine human IgM and IgG binding to tissues. Flow cytometric analysis was used to determine Gal and NeuGc expression on cultured CECs and AECs and to measure human IgM/IgG binding to these cells. Results Both Gal and NeuGc were detected on WT pig corneas and aortas. Although GTKO pigs expressed NeuGc, neither human nor GTKO/NeuGcKO pigs expressed Gal or NeuGc. Human IgM/IgG binding to corneas and aortas from GTKO and GTKO/NeuGcKO pigs was reduced compared to binding to WT pigs. Human antibody binding to GTKO/NeuGcKO AECs was significantly less than to GTKO AECs, but there was no significant difference in binding between GTKO and GTKO/NeuGcKO CECs. Conclusions The absence of NeuGc on GTKO aortic tissue and AECs is associated with reduced human antibody binding, and possibly will provide better outcome in clinical xenotransplantation using vascularized organs. For clinical corneal xenotransplantation, the absence of NeuGc expression on GTKO/NeuGcKO pig corneas may not prove an advantage over GTKO corneas. PMID:26418433

The importance of echocardiography in transcatheter aortic valve implantation.

PubMed

Bilen, Emine; Sari, Cenk; Durmaz, Tahir; Keleş, Telat; Bayram, Nihal A; Akçay, Murat; Ayhan, Hüseyin M; Bozkurt, Engin

2014-01-01

Valvular heart diseases cause serious health problems in Turkey as well as in Western countries. According to a study conducted in Turkey, aortic stenosis (AS) is second after mitral valve disease among all valvular heart diseases. AS is frequently observed in elderly patients who have several cardiovascular risk factors and comorbidities. In symptomatic severe AS, surgical aortic valve replacement (AVR) is a definitive treatment. However, in elderly patients with left ventricular dysfunction and comorbidities, the risk of operative morbidity and mortality increases and outweighs the gain obtained from AVR surgery. As a result, almost one-third of the patients with serious AS are considered ineligible for surgery. Transcatheter aortic valve implantation (TAVI) is an effective treatment in patients with symptomatic severe AS who have high risk for conventional surgery. Since being performed for the first time in 2002, with a procedure success rate reported as 95% and a mortality rate of 5%, TAVI has become a promising method. Assessment of vascular anatomy, aortic annular diameter, and left ventricular function may be useful for the appropriate selection of patients and may reduce the risk of complications. Cardiac imaging methods including 2D and 3D echocardiography and multidetector computed tomography are critical during the evaluation of suitable patients for TAVI as well as during and after the procedure. In this review, we describe the role of echocardiography methods in clinical practice for TAVI procedure in its entirety, i.e. from patient selection to guidance during the procedure, and subsequent monitoring. © 2013, Wiley Periodicals, Inc.

First long-term evidence supporting endovascular repair of abdominal aortic aneurysms.

PubMed

Indes, Jeffrey E; Muhs, Bart E; Dardik, Alan

2013-04-01

The traditional method of treating abdominal aortic aneurysms with open surgical repair has been steadily replaced by endovascular repair, thought to be a more minimally invasive approach. It is not known, however, whether the endovascular approach is truly less invasive for operative physiology; in addition, this approach has a different spectrum of complications. As such, it is uncertain whether elective endovascular repair of nonruptured aortic aneurysms reduces long-term morbidity and mortality compared with traditional open approaches. In this article, the authors evaluate a recent publication investigating long-term outcomes of a prospective randomized multicenter trial evaluating patients with asymptomatic abdominal aortic aneurysms treated with either endovascular or open repair, and discuss the results in the context of current evidence.

The numerical simulation study of hemodynamics of the new dense-mesh stent

NASA Astrophysics Data System (ADS)

Ma, Jiali; Yuan, Zhishan; Yu, Xuebao; Feng, Zhaowei; Miao, Weidong; Xu, Xueli; Li, Juntao

2017-09-01

The treatment of aortic aneurysm in new dense mesh stent is based on the principle of hemodynamic changes. But the mechanism is not yet very clear. This paper analyzed and calculated the hemodynamic situation before and after the new dense mesh stent implanting by the method of numerical simulation. The results show the dense mesh stent changed and impacted the blood flow in the aortic aneurysm. The changes include significant decrement of blood velocity, pressure and shear forces, while ensuring blood can supply branches, which means the new dense mesh stent's hemodynamic mechanism in the treatment of aortic aneurysm is clearer. It has very important significance in developing new dense mesh stent in order to cure aortic aneurysm.

Endovascular stenting of a chronic ruptured type B thoracic aortic dissection, a second chance: a case report.

PubMed

Arshad, Ali; Khan, Sumaira L; Whitaker, Simon C; Macsweeney, Shane T

2008-02-07

We aim to highlight the need for awareness of late complications of endovascular thoracic aortic stenting and the need for close follow-up of patients treated by this method. We report the first case in the English literature of an endovascular repair of a previously stented, ruptured chronic Stanford type B thoracic aortic dissection re-presenting with a type III endoleak of the original repair. Endovascular thoracic stenting is now a widely accepted technique for the treatment of thoracic aortic dissection and its complications. Long term follow up is necessary to ensure that late complications are identified and treated appropriately. In this case of type III endoleak, although technically challenging, endovascular repair was feasible and effective.

Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells.

PubMed

Schramm, D D; Wang, J F; Holt, R R; Ensunsa, J L; Gonsalves, J L; Lazarus, S A; Schmitz, H H; German, J B; Keen, C L

2001-01-01

Polyphenolic phytochemicals inhibit vascular and inflammatory processes that contribute to disease. These effects are hypothesized to result from polyphenol-mediated alterations in cellular eicosanoid synthesis. The objective was to determine and compare the ability of cocoa procyanidins to alter eicosanoid synthesis in human subjects and cultured human aortic endothelial cells. After an overnight fast, 10 healthy subjects (4 men and 6 women) consumed 37 g low-procyanidin (0.09 mg/g) and high-procyanidin (4.0 mg/g) chocolate; the treatments were separated by 1 wk. The investigation had a randomized, blinded, crossover design. Plasma samples were collected before treatment and 2 and 6 h after treatment. Eicosanoids were quantitated by enzyme immunoassay. Endothelial cells were treated in vitro with procyanidins to determine whether the effects of procyanidin in vivo were associated with procyanidin-induced alterations in endothelial cell eicosanoid synthesis. Relative to the effects of the low-procyanidin chocolate, high-procyanidin chocolate induced increases in plasma prostacyclin (32%; P<0.05) and decreases in plasma leukotrienes (29%; P<0.04). After the in vitro procyanidin treatments, aortic endothelial cells synthesized twice as much 6-keto-prostaglandin F(1alpha) (P<0.01) and 16% less leukotriene (P<0.05) as did control cells. The in vitro and in vivo effects of procyanidins on plasma leukotriene-prostacyclin ratios in culture medium were also comparable: decreases of 58% and 52%, respectively. Data from this short-term investigation support the concept that certain food-derived flavonoids can favorably alter eicosanoid synthesis in humans, providing a plausible hypothesis for a mechanism by which they can decrease platelet activation in humans.

The effect of demographic features on aortic arch anatomy and its role in the etiology of cerebrovascular disease

PubMed Central

İnanç, Yılmaz; İnanç, Yusuf; Ay, Halil

2018-01-01

Purpose The aim of this study was to retrospectively evaluate the distribution of aortic arches, the relationship with demographic characteristics, and the results of carotid and vertebral artery stenting procedures in patients diagnosed with cerebrovascular disease through the intra-arterial digital subtraction angiography (DSA) technique. Methods A retrospective examination was performed on 288 patients diagnosed with cerebrovascular disease, who underwent DSA in the Department of Neurology of Gaziantep University Medical Faculty and Kahramanmaraş¸ Sütçü Imam University Medical Faculty. The patients were examined in respect of demographic features and aortic arch anatomic structure characteristics. All demographic characteristics, DSA, carotid, and vertebral artery stent results were recorded. Results The patients comprised 60.1% males and 39.9% females with a mean age of 58.25 years. Type 2 aortic arch was found in 175 (60.7%) patients, Type 2 aortic arch in 99 (34.3%) patients, and Type 3 aortic arch in 14 (4.8%) patients. The right carotid artery stenosis rate was found to be higher in patients with Type 2 aortic arch (P=0.013). When the patients were evaluated according to the presence of a bovine arch, there was no significant difference in terms of age, carotid, and vertebral artery lesions (P>0.05). Conclusion The aortic arch and its branching properties were not found to have a direct effect on increased risk of cerebrovascular disease or stenting rates. This study can be considered to raise awareness for new studies to demonstrate the effect of aortic arch anatomic differences on cerebrovascular diseases. PMID:29302189

The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease

PubMed Central

Adenwalla, Sherna F.; Leone, Francesca M.T.; Burton, James O.; McCann, Gerry P.

2017-01-01

Abstract Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work. PMID:28852490

Bare Metal Stenting for Endovascular Exclusion of Aortic Arch Thrombi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahnken, Andreas H., E-mail: mahnken@med.uni-marburg.de; Hoffman, Andras; Autschbach, Ruediger

BackgroundAortic thrombi in the ascending aorta or aortic arch are rare but are associated with a relevant risk of major stroke or distal embolization. Although stent grafting is commonly used as a treatment option in the descending aorta, only a few case reports discuss stenting of the aortic arch for the treatment of a thrombus. The use of bare metal stents in this setting has not yet been described.MethodsWe report two cases of ascending and aortic arch thrombus that were treated by covering the thrombus with an uncovered stent. Both procedures were performed under local anesthesia via a femoral approach.more » A femoral cutdown was used in one case, and a total percutaneous insertion was possible in the second case.ResultsBoth procedures were successfully performed without any periprocedural complications. Postoperative recovery was uneventful. In both cases, no late complications or recurrent embolization occurred at midterm follow-up, and control CT angiography at 1 respectively 10 months revealed no stent migration, freely perfused supra-aortic branches, and no thrombus recurrence.ConclusionTreating symptomatic thrombi in the ascending aorta or aortic arch with a bare metal stent is feasible. This technique could constitute a minimally invasive alternative to a surgical intervention or complex endovascular therapy with fenestrated or branched stent grafts.« less

Litigation in nontraumatic aortic diseases--a tempest in the malpractice maelstrom.

PubMed

Elefteriades, John A; Barrett, Peter W; Kopf, Gary S

2008-01-01

Physicians are vulnerable to highly litigated thoracic aortic diseases. On the basis of a review of litigated cases, we aim to determine legally protective strategies for physicians and methods to improve treatment. Thirty-three nontraumatic, thoracic aorta-related legal cases were analyzed. Twenty-three patients (69.7%) had dissections (21 ascending, 2 descending), 8 (24.2%) had aneurysms and 2 had miscellaneous other phenomena (1 coarctation and 1 iatrogenic descending aortic rupture). The adverse event was death in 30 (90.9%) patients and paraplegia or stroke in 3 (9.1%). Allegations included: failure/delay in diagnosis (19), delay in surgery (4), error in surgical technique (5), failure to prevent paraplegia (2) and miscellaneous (3). Medical treatment was retrospectively judged suboptimal in 22 cases (66.6%) for reasons consonant with allegations. Aortic disease can be diagnostically elusive, as 'the great masquerader'. Emergency physicians must maintain a high index of suspicion for aneurysm and dissection. The D-dimer test can effectively rule out aortic dissection. 'Triple rule-out' CT scans should be performed liberally. CT scan readers must remember to evaluate the aorta. Operating room administrators must be aware that postponing a scheduled thoracic aortic case may result in interim rupture and consequent litigation. With virulent thoracic aortic diseases, adverse outcome itself does not imply substandard care. 2007 S. Karger AG, Basel

Computational Assessment of Blood Flow Heterogeneity in Peritoneal Dialysis Patients' Cardiac Ventricles

PubMed Central

Kharche, Sanjay R.; So, Aaron; Salerno, Fabio; Lee, Ting-Yim; Ellis, Chris; Goldman, Daniel; McIntyre, Christopher W.

2018-01-01

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status. PMID:29867555

Regional cerebral perfusion for surgical correction of neonatal aortic arch obstruction.

PubMed

Zhang, Hui; Cheng, Pei; Hou, Jia; Li, Lei; Liu, Hu; Liu, Ruifang; Ji, Bingyang; Luo, Yi

2009-05-01

One-stage repair of aortic arch obstruction and associated cardiac anomalies is a surgical challenge in infants.The purpose of the present study is to review the current outcome using regional cerebral perfusion (RCP) during a procedure correcting interrupted aortic arch (IAA) and also isolated aortic coarctation (CoA) and CoA combined with hypoplastic aortic arch (CoA-HyAA) in our center. Between January 2007 and July 2008, 24 infant patients with interrupted aortic arch (IAA) (n=3), isolated aortic coarctation (iCoA) (n=9) and aortic coarctation with hypoplastic aortic arch (CoA-HyAA) (n=12) underwent one-stage surgical correction in our hospital. End-to-end anastomosis was employed in 12 infants (IAA n=3 and iCoA n=9); for the other 12 patients with CoA-HyAA, an end-to-end extended anastomosis was used in 8 cases, end-to-side anastomosis in 2 cases, and composite heterologous pericardial patch in 2 cases. RCP with 40 mL/kg/min through the innominate artery during aortic arch reconstruction was employed for all pediatric patients. One single-dose histidine-ketoglutarate-tryptophan (HTK) solution was used for myocardial protection during CPB. Cardiopulmonary bypass time and aortic cross-clamp time were 165.6+/-32.4 min and 81.7+/-30.0 min, respectively. The mean regional cerebral perfusion time was 31.0+/-10.6 min; lowest nasopharyngeal temperature was 19.1+/-1.1 degrees C. Operative mortality rate in both groups was 8.3%. Mean follow-up was 10.5+/-4.8 months. There was no late mortality or postoperative neurologic, renal or hepatic complications. All patients are asymptomatic and are developing normally. One-stage total arch repair using the RCP technique is an excellent method that may minimize neurologic and renal complications. Our surgical strategy for arch anomaly has a low rate of residual and recurrent coarctation when performed in these infants.

Vehicular Causation Factors and Conceptual Design Modifications to Reduce Aortic Strain in Numerically Reconstructed Real World Nearside Lateral Automotive Crashes

PubMed Central

Yang, King H.

2015-01-01

Aortic injury (AI) leading to disruption of the aorta is an uncommon but highly lethal consequence of trauma in modern society. Most recent estimates range from 7,500 to 8,000 cases per year from a variety of causes. It is observed that more than 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest cavity. It is evident that effective means of substantially improving the outcome of motor vehicle crash-induced AIs is by preventing the injury in the first place. In the current study, 16 design of computer experiments (DOCE) were carried out with varying levels of principal direction of force (PDOF), impact velocity, impact height, and impact position of the bullet vehicle combined with occupant seating positions in the case vehicle to determine the effects of these factors on aortic injury. Further, a combination of real world crash data reported in the Crash Injury Research and Engineering Network (CIREN) database, Finite Element (FE) vehicle models, and the Wayne State Human Body Model-II (WSHBM-II) indicates that occupant seating position, impact height, and PDOF, in that order play, a primary role in aortic injury. PMID:26448781

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.

PubMed

Huk, Danielle J; Hammond, Harriet L; Kegechika, Hiroyuki; Lincoln, Joy

2013-02-01

Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

Aortic Valve Endocarditis in a Dog Due to Bartonella clarridgeiae

PubMed Central

Chomel, Bruno B.; Mac Donald, Kristin A.; Kasten, Rickie W.; Chang, Chao-Chin; Wey, Aaron C.; Foley, Janet E.; Thomas, William P.; Kittleson, Mark D.

2001-01-01

We report the first documented case of endocarditis associated with Bartonella clarridgeiae in any species. B. clarridgeiae was identified as a possible etiological agent of human cat scratch disease. Infective vegetative valvular aortic endocarditis was diagnosed in a 2.5-year-old male neutered boxer. Historically, the dog had been diagnosed with a systolic murmur at 16 months of age and underwent balloon valvuloplasty for severe valvular aortic stenosis. Six months later, the dog was brought to a veterinary hospital with an acute third-degree atrioventricular block and was diagnosed with infective endocarditis. The dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious, gram-negative organism 8 days after being plated. Phenotypic and genotypic characterization of the isolate, including partial sequencing of the citrate synthase (gltA) and 16S rRNA genes indicated that this organism was B. clarridgeiae. DNA extraction from the deformed aortic valve and the healthy pulmonic valve revealed the presence of B. clarridgeiae DNA only from the diseased valve. No Borrelia burgdorferi or Ehrlichia sp. DNA could be identified. Using indirect immunofluorescence tests, the dog was seropositive for B. clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, or Coxiella burnetii. PMID:11574571

[Comparison of aortic valve dysfunction and ascending aorta dimension between patients with different bicuspid aortic valve morphology].

PubMed

Ren, X S; Yu, Y T; Liu, K; Hou, Z H; Gao, Y; Yin, W H; Lyu, B

2017-06-24

Objective: To compare the characteristics of aortic valve dysfunction and ascending aorta dimension in patients with different bicuspid aortic valve (BAV) morphology. Methods: A total of 197 patients who underwent aortic valve replacement between April 2014 and March 2015 and were diagnosed with BAV by pathology were included, and their clinical data were retrospectively analyzed. Patients were divided into raphe(+) group(109 cases) and raphe(-) group(88 cases) according to the presence or absence of raphe, and L-R group(fusion of left and right cusp, 125 cases) and L/R-N group(fusion of left or right and noncoronary cusp, 72 cases) according to fusion type of the cusps. The characteristics of aortic valve dysfunction and ascending aorta dimension in patients with different BAV morphology were compared. Results: (1) Aortic stenosis incidence was lower in raphe(+) group than in raphe(-) group(22.9%(25/109) vs. 69.3%(61/88), P <0.001). Aortic regurgitation incidence was higher in raphe(+) group than in raphe(-) group (61.5%(67/109) vs. 22.7%(20/88), P <0.001). Incidence of type 1 of aortic root dilation was higher in raphe(+) group than in raphe(-) group (23.9%(26/109)vs.10.2%(9/88), P =0.024). (2) Aortic stenosis incidence was lower in L-R group than in L/R-N group(29.6%(37/125) vs. 68.1%(49/72), P <0.001). Aortic regurgitation incidence was higher in L-R group than in L/R-N group (59.2%(74/125) vs. 18.1%(13/72), P <0.001). Incidence of type 3 of aortic root dilation was lower in L-R group than in L/R-N group(10.4%(13/125) vs. 37.5%(27/72), P =0.006). (3) Aortic stenosis incidence was lower in L-R patients than in L/R-N patients(15.1%(13/86)vs. 52.2%(12/23), P =0.001), and aortic regurgitation incidence was higher in L-R patients than in L/R-N patients in raphe(+) group(73.3%(63/86)vs. 17.4%(4/23), P <0.001). Conclusion: There is significant difference in the type of valvular dysfunction and ascending aorta dilatation in patients with different morphological characteristics of BAV.

[Value of bedside echocardiography in diagnosis and risk assessment of in-hospital death for patients with Stanford type A aortic dissection].

PubMed

Wang, H J; Xiao, Z Y; Gu, G R; Xue, Y; Shao, M; Deng, Z; Tao, Z G; Yao, C L; Tong, C Y

2017-11-24

Objective: To investigate the value of bedside echocardiography in diagnosis and risk assessment of in-hospital death of patients with Stanford type A aortic dissection. Methods: The clinical data of 229 patients with Stanford type A aortic dissection diagnosed by CT angiography in Zhongshan Hospital affiliated to Fudan University between January 2009 and January 2016 were retrospectively analyzed. The patients were divided into survival group(191 cases)and non-survival group(38 cases)according to presence or absence of in-hospital death. The bedside echocardiography features were analyzed, and influence factors of in-hospital death were determined by multivariate logistic regression analysis. Results: (1) Compared with the survival group, the non-survival group had lower surgery rate (60.52%(23/38) vs. 85.34%(163/191), P <0.01). Age, gender and Debakey classification were similar between survival group and death group (all P >0.05). (2) The bedside echocardiography results showed that prevalence of aortic valve involvement(65.79%(25/38) vs.34.03%(65/191), P <0.01) and severe aortic regurgitation (44.74%(17/38) vs. 14.14%(27/191), P <0.01) were significantly higher in non-survival group than in survival group. The non-survival group had larger aortic root diameter than the survival group ((55.5±6.4)mm vs. (42.3±7.8)mm, P <0.01). There were no significant differences in pericardial effusion, expansion of aortic sinus, and left ventricular ejection fraction between survival group and non-survival group (all P >0.05). (3) The multivariate logistic regression analysis showed that aortic valve involvement( OR =3.275, 95% CI 1.290-8.313, P <0.05), aortic root diameter( OR =1.202, 95% CI 1.134-1.275, P <0.01), and surgery ( OR =0.224, 95% CI 0.079-0.629, P <0.01) were independent risk factors for in-hospital death in patients with Stanford type A aortic dissection. Conclusions: Bedside echocardiography has significant diagnostic value for Stanford type A aortic dissection. Aortic valve involvement, enlargement of aortic root diameter and without surgery are independent risk factors for patients with Stanford type A aortic dissection.

Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

PubMed Central

Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

2009-01-01

Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

Aortic Replacement with Sutureless Intraluminal Grafts

PubMed Central

Lemole, Gerald M.

1990-01-01

To avoid the anastomotic complications and long cross-clamp times associated with standard suture repair of aortic lesions, we have implanted sutureless intraluminal grafts in 122 patients since 1976. Forty-nine patients had disorders of the ascending aorta, aortic arch, or both: their operative mortality was 14% (7 patients), and the group's 5-year actuarial survival rate has been 64%. There have been no instances of graft dislodgment, graft infection, aortic bleeding, or pseudoaneurysm formation. Forty-two patients had disorders of the descending aorta and thoracoabdominal aorta: their early mortality was 10% (4 patients), and the group's 5-year actuarial survival rate has been 56%. There was 1 early instance of graft dislodgment, but no pseudoaneurysm formation, graft erosion, aortic bleeding, intravascular hemolysis, or permanent deficits in neurologic, renal, or vascular function. Thirty-one patients had the sutureless intraluminal graft implanted in the abdominal aortic position: their early mortality was 6% (2 patients), and the 5-year actuarial survival rate for this group has been 79%. There were no instances of renal failure, ischemic complication, postoperative paraplegia, pseudoaneurysm, or anastomotic true aneurysm. Our recent efforts have been directed toward developing an adjustable spool that can adapt to the widest aorta or the narrowest aortic arch vessel; but in the meanwhile, the present sutureless graft yields shorter cross-clamp times, fewer intraoperative complications, and both early and late results as satisfactory as those afforded by traditional methods of aortic repair. (Texas Heart Institute Journal 1990; 17:302-9) Images PMID:15227522

Time-Resolved Three-Dimensional Contrast-Enhanced Magnetic Resonance Angiography in Patients with Chronic Expanding and Stable Aortic Dissections

PubMed Central

Trojan, Michael; Kotelis, Drosos; Müller-Eschner, Matthias; Partovi, Sasan; Fink, Christian; Karmonik, Christof; Böckler, Dittmar; Kauczor, Hans-Ulrich; von Tengg-Kobligk, Hendrik

2017-01-01

Objective To prospectively evaluate our hypothesis that three-dimensional time-resolved contrast-enhanced magnetic resonance angiography (TR-MRA) is able to detect hemodynamic alterations in patients with chronic expanding aortic dissection compared to stable aortic dissections. Materials and Methods 20 patients with chronic or residual aortic dissection in the descending aorta and patent false lumen underwent TR-MRA of the aorta at 1.5 T and repeated follow-up imaging (mean follow-up 5.4 years). 7 patients showed chronic aortic expansion and 13 patients had stable aortic diameters. Regions of interest were placed in the nondissected ascending aorta and the false lumen of the descending aorta at the level of the diaphragm (FL-diaphragm level) resulting in respective time-intensity curves. Results For the FL-diaphragm level, time-to-peak intensity and full width at half maximum were significantly shorter in the expansion group compared to the stable group (p = 0.027 and p = 0.003), and upward and downward slopes of time-intensity curves were significantly steeper (p = 0.015 and p = 0.005). The delay of peak intensity in the FL-diaphragm level compared to the nondissected ascending aorta was significantly shorter in the expansion group compared to the stable group (p = 0.01). Conclusions 3D TR-MRA detects significant alterations of hemodynamics within the patent false lumen of chronic expanding aortic dissections compared to stable aortic dissections. PMID:29317855

Contemporary patterns of surgery and outcomes for aortic coarctation: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database

PubMed Central

Ungerleider, Ross M.; Pasquali, Sara K.; Welke, Karl F.; Wallace, Amelia S.; Ootaki, Yoshio; Quartermain, Michael D.; Williams, Derek A.; Jacobs, Jeffrey P.

2013-01-01

Objective The objective of this study was to describe characteristics and early outcomes across a large multicenter cohort undergoing coarctation or hypoplastic aortic arch repair. Methods Patients undergoing coarctation or hypoplastic aortic arch repair (2006–2010) as their first cardiovascular operation in the Society of Thoracic Surgeons Congenital Heart Surgery Database were included. Group 1 patients consisted of those with coarctation or hypoplastic aortic arch without ventricular septal defect (coarctation or hypoplastic aortic arch, isolated); group 2, coarctation or hypoplastic aortic arch with ventricular septal defect (coarctation or hypoplastic aortic arch, ventricular septal defect); and group 3, coarctation or hypoplastic aortic arch with other major cardiac diagnoses (coarctation or hypoplastic aortic arch, other). Results The cohort included 5025 patients (95 centers): group 1, 2705 (54%); group 2, 840 (17%); and group 3, 1480 (29%). Group 1 underwent coarctation or hypoplastic aortic arch repair at an older age than groups 2 and 3 (groups 1, 2, and 3, 75%, 99%, and 88% < 1 year old, respectively; P<.0001). The most common operative techniques for coarctation or hypoplastic aortic arch repair (group 1) were end-to-end (33%) or extended end-to-end (56%) anastomosis. Overall mortality was 2.4%, and was 1%, 2.5%, and 4.8% for groups 1, 2, and 3 respectively (P < .0001). Ventricular septal defect management strategies for group 2 patients included ventricular septal defect closure (n = 211, 25%), pulmonary artery band (n = 89, 11%), or no intervention (n = 540, 64%) without significant difference in mortality (4%, 1%, 2%; P = .15). Postoperative complications occurred in 36% of patients overall and were more common in groups 2 and 3. There were no occurrences of spinal cord injury (0/973). Conclusions In the current era, primary coarctation or hypoplastic aortic arch repair is performed predominantly in neonates and infants. Overall mortality is low, although those with concomitant defects are at risk for higher morbidity and mortality. The risk of spinal cord injury is lower than previously reported. PMID:23098750

Early outcomes of transcatheter aortic valve replacement in patients with severe aortic stenosis: single center experience

PubMed Central

Bozkurt, Engin; Keleş, Telat; Durmaz, Tahir; Akçay, Murat; Ayhan, Hüseyin; Bayram, Nihal Akar; Aslan, Abdullah Nabi; Baştuğ, Serdal; Bilen, Emine

2014-01-01

Introduction Transcatheter aortic valve implantation is a promising alternative to high risk surgical aortic valve replacement. The procedure is mainly indicated in patients with severe symptomatic aortic stenosis who cannot undergo surgery or who are at very high surgical risk. Aim Description early results of our single-center experience with balloon expandable aortic valve implantation. Material and methods Between July 2011 and August 2012, we screened in total 75 consecutive patients with severe aortic stenosis and high risk for surgery. Twenty-one of them were found ineligible for transcatheter aortic valve implantation (TAVI) because of various reasons, and finally we treated a total of 54 patients with symptomatic severe aortic stenosis (AS) who could not be treated by open heart surgery (inoperable) because of high-risk criteria. The average age of the patients was 77.4 ±7.1; 27.8% were male and 72.2% were female. The number of patients in NYHA class II was 7 while the number of patients in class III and class IV was 47. Results The average mortality score of patients according to the STS scoring system was 8.5%. Pre-implantation mean and maximal aortic valve gradients were measured as 53.2 ±14.1 mm Hg and 85.5 ±18.9 mm Hg, respectively. Post-implantation mean and maximal aortic valve gradients were 9.0 ±3.0 and 18.2 ±5.6, respectively (p < 0.0001). The left ventricular ejection fraction was calculated as 54.7 ±14.4% before the operation and 58.0 ±11.1% after the operation (p < 0.0001). The duration of discharge after the operation was 5.29 days, and a statistically significant correlation between the duration of discharge after the operation and STS was found (r = 0385, p = 0.004). Conclusions We consider that with decreasing cost and increasing treatment experience, TAVI will be used more frequently in broader indications. Our experience with TAVI using the Edwards-Sapien XT (Edwards Lifesciences, Irvine, CA) devices suggests that this is an effective and relatively safe procedure for the treatment of severe aortic stenosis in suitable patients. PMID:25061453

Optical coherence tomography assessment of vessel wall degradation in thoracic aortic aneurysms

NASA Astrophysics Data System (ADS)

Real, Eusebio; Eguizabal, Alma; Pontón, Alejandro; Díez, Marta Calvo; Fernando Val-Bernal, José; Mayorga, Marta; Revuelta, José M.; López-Higuera, José M.; Conde, Olga M.

2013-12-01

Optical coherence tomography images of human thoracic aorta from aneurysms reveal elastin disorders and smooth muscle cell alterations when visualizing the media layer of the aortic wall. These disorders can be employed as indicators for wall degradation and, therefore, become a hallmark for diagnosis of risk of aneurysm under intraoperative conditions. Two approaches are followed to evaluate this risk: the analysis of the reflectivity decay along the penetration depth and the textural analysis of a two-dimensional spatial distribution of the aortic wall backscattering. Both techniques require preprocessing stages for the identification of the air-sample interface and for the segmentation of the media layer. Results show that the alterations in the media layer of the aortic wall are better highlighted when the textural approach is considered and also agree with a semiquantitative histopathological grading that assesses the degree of wall degradation. The correlation of the co-occurrence matrix attains a sensitivity of 0.906 and specificity of 0.864 when aneurysm automatic diagnosis is evaluated with a receiver operating characteristic curve.

Abdominal aortic aneurysm: novel mechanisms and therapies.

PubMed

Davis, Frank M; Rateri, Debra L; Daugherty, Alan

2015-11-01

Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β, and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in AAA development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight into the development of a medical treatment for this disease.

Effect of choline magnesium trisalicylate on prostacyclin production by isolated vascular tissue of the rat.

PubMed

Levy, J V

1983-01-15

Choline Magnesium Trisalicylate (Trilisate), in therapeutic concentrations of 5, 10, 15 and 30 mg/100 ml, did not significantly affect production of prostacyclin-like (PGI2) substance by rat aortic tissue in vitro. The ED50 for inhibition of aorta PGI2-like substance production by Trilisate was 1,200 mg/100 ml. This is approximately 40 times the maximum therapeutic blood concentration achieved in humans. Choline or Magnesium salicylate produced slight but insignificant inhibition of PGI2-like substance production by rat aortic tissue in vitro. The ED50 for ibuprofen (Motrin) for inhibition of PGI2-like production of rat aortic rings was 0.65-0.92 mg/100 ml. Injection of Choline Magnesium Trisalicylate into rats (124, 250, 500 mg/kg I.P.) did not affect the normal production of PGI2-like substance of aortic tissue obtained one hour after in vivo treatment. These results suggest this anti-inflammatory salicylate does not adversely affect PGI2-like production by blood vessels, in concentrations associated with therapeutic effects in man.

In vivo geometry of the kissing stent and covered endovascular reconstruction of the aortic bifurcation configurations in aortoiliac occlusive disease

PubMed Central

Ter Mors, Thijs G; Slump, Cornelis H; Geelkerken, Robert H; Holewijn, Suzanne; Reijnen, Michel MPJ

2017-01-01

Objectives Various configurations of kissing stent (KS) configurations exist and patency rates vary. In response the covered endovascular reconstruction of the aortic bifurcation configuration was designed to minimize mismatch and improve outcome. The aim of the current study is to compare geometrical mismatch of kissing stent with the covered endovascular reconstruction of the aortic bifurcation configuration in vivo. Methods Post-operative computed tomographic data and patient demographics from 11 covered endovascular reconstruction of the aortic bifurcation and 11 matched kissing stent patients were included. A free hand region of interest and ellipse fitting method were applied to determine mismatch areas and volumes. Conformation of the stents to the vessel wall was expressed using the D-ratio. Results Patients were mostly treated for Rutherford category 2 and 3 (64%) with a lesion classification of TASC C and D in 82%. Radial mismatch area and volume for the covered endovascular reconstruction of the aortic bifurcation group was significantly lower compared to the kissing stent configuration (P < 0.05). The D-ratio did not significantly differ between groups. Measurements were performed with good intra-class correlation. There were no significant differences in the post-procedural aortoiliac anatomy. Conclusions The present study shows that radial mismatch exists in vivo and that large differences in mismatch exist, in favour of the covered endovascular reconstruction of the aortic bifurcation configuration. Future research should determine if the decreased radial mismatch results in improved local flow profiles and subsequent clinical outcome. PMID:28530484

In vivo geometry of the kissing stent and covered endovascular reconstruction of the aortic bifurcation configurations in aortoiliac occlusive disease.

PubMed

Groot Jebbink, Erik; Ter Mors, Thijs G; Slump, Cornelis H; Geelkerken, Robert H; Holewijn, Suzanne; Reijnen, Michel Mpj

2017-12-01

Objectives Various configurations of kissing stent (KS) configurations exist and patency rates vary. In response the covered endovascular reconstruction of the aortic bifurcation configuration was designed to minimize mismatch and improve outcome. The aim of the current study is to compare geometrical mismatch of kissing stent with the covered endovascular reconstruction of the aortic bifurcation configuration in vivo. Methods Post-operative computed tomographic data and patient demographics from 11 covered endovascular reconstruction of the aortic bifurcation and 11 matched kissing stent patients were included. A free hand region of interest and ellipse fitting method were applied to determine mismatch areas and volumes. Conformation of the stents to the vessel wall was expressed using the D-ratio. Results Patients were mostly treated for Rutherford category 2 and 3 (64%) with a lesion classification of TASC C and D in 82%. Radial mismatch area and volume for the covered endovascular reconstruction of the aortic bifurcation group was significantly lower compared to the kissing stent configuration ( P < 0.05). The D-ratio did not significantly differ between groups. Measurements were performed with good intra-class correlation. There were no significant differences in the post-procedural aortoiliac anatomy. Conclusions The present study shows that radial mismatch exists in vivo and that large differences in mismatch exist, in favour of the covered endovascular reconstruction of the aortic bifurcation configuration. Future research should determine if the decreased radial mismatch results in improved local flow profiles and subsequent clinical outcome.

Multidisciplinary Treatment Approach for Prosthetic Vascular Graft Infection in the Thoracic Aortic Area

PubMed Central

Watanabe, Yoshinori

2015-01-01

Prosthetic vascular graft infection in the thoracic aortic area is a rare but serious complication. Adequate management of the complication is essential to increase the chance of success of open surgery. While surgical site infection is suggested as the root cause of the complication, it is also related to decreased host tolerance, especially as found in elderly patients. The handling of prosthetic vascular graft infection has been widely discussed to date. This paper mainly provides a summary of literature reports published within the past 5 years to discuss issues related to multidisciplinary treatment approaches, including surgical site infection, timing of onset, diagnostic methods, causative pathogens, auxiliary diagnostic methods, antibiotic treatment, anti-infective structures of vascular prostheses, surgical treatment, treatment strategy against infectious aortic aneurysms, future surgical treatment, postoperative systemic therapy, and antimicrobial stewardship. A thorough understanding of these issues will enable us to prevent prosthetic vascular graft infection in the thoracic aortic area as far as possible. In the event of its occurrence, the early introduction of appropriate treatment is expected to cure the disease without worsening of the underlying pathological condition. PMID:26356686

Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance

PubMed Central

Vassiliou, Vassilios S.; Flynn, Paul D.; Raphael, Claire E.; Newsome, Simon; Khan, Tina; Ali, Aamir; Halliday, Brian; Studer Bruengger, Annina; Malley, Tamir; Sharma, Pranev; Selvendran, Subothini; Aggarwal, Nikhil; Sri, Anita; Berry, Helen; Donovan, Jackie; Lam, Willis; Auger, Dominique; Cook, Stuart A.; Pennell, Dudley J.; Prasad, Sanjay K.

2017-01-01

Background Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. Methods A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). Results Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). Conclusion There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis. PMID:28704465

Insurance Status is Associated with Acuity of Presentation and Outcomes for Thoracic Aortic Operations

PubMed Central

Andersen, Nicholas D.; Brennan, J. Matthew; Zhao, Yue; Williams, Judson B.; Williams, Matthew L.; Smith, Peter K.; Scarborough, John E.; Hughes, G. Chad

2014-01-01

Background Non-elective procedure status is the greatest risk factor for postoperative morbidity and mortality in patients undergoing thoracic aortic operations. We hypothesized that uninsured patients were more likely to require non-elective thoracic aortic operation due to decreased access to preventative care and elective surgical services. Methods and Results An observational study of the Society of Thoracic Surgeons Database identified 51,282 patients who underwent thoracic aortic surgery between 2007–2011 at 940 North American centers. Patients were stratified by insurance status (private insurance, Medicare, Medicaid, other insurance, or uninsured) as well as age < 65 years or age ≥ 65 years to account for differences in Medicare eligibility. The need for non-elective thoracic aortic operation was highest for uninsured patients (71.7%) and lowest for privately insured patients (36.6%). The adjusted risks of non-elective operation were increased for uninsured patients (adjusted risk ratio [ARR], 1.77; 95% confidence interval [CI], 1.70–1.83 for age < 65 years; ARR, 1.46; 95% CI, 1.29–1.62 for age ≥ 65 years) as well as Medicaid patients age < 65 years (ARR, 1.18; 95% CI, 1.10–1.26) when compared to patients with private insurance. The adjusted odds of major morbidity and/or mortality were further increased for all patients age < 65 years without private insurance (ARRs between 1.13 and 1.27). Conclusions Insurance status was associated with acuity of presentation and major morbidity and mortality for thoracic aortic operations. Efforts to reduce insurance-based disparities in the care of patients with thoracic aortic disease appear warranted and may reduce the incidence of aortic emergencies and improve outcomes after thoracic aortic surgery. PMID:24714600

Spontaneous aortic dissecting hematoma in two dogs.

PubMed

Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William

2005-09-01

This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

Inhibition of angiogenic attributes by decursin in endothelial cells and ex vivo rat aortic ring angiogenesis model.

PubMed

Bhat, Tariq A; Moon, Jung S; Lee, Sookyeon; Yim, Dongsool; Singh, Rana P

2011-11-01

The present study was undertaken to observe the inhibition of angiogenesis by decursin. It was the first time to show that decursin offered strong anti-angiogenic activities under the biologically relevant growth (with serum) conditions. Decursin significantly inhibited human umbilical vein endothelial cell (HUVEC) proliferation concomitant with G1 phase cell cycle arrest. Decursin also inhibited HUVEC-capillary tube formation and invasion/migration in a dose-dependant manner which was associated with the suppression of matrix metalloproteinase (MMP) -2 and -9 activities. Decursin suppressed angiogenesis in ex vivo rat aortic ring angiogenesis model where it significantly inhibited blood capillary-network sprouting from rat aortic sections. Taken together, these findings suggested anti-angiogenic activity of decursin in biologically relevant condition, and warrants further pre-clinical studies for its potential clinical usefulness.

Aberrant left subclavian artery occlusion in right-sided aortic artery associated with left cerebral infarction: A case report.

PubMed

Tempaku, Akira; Kuroiwa, Terumasa; Nishio, Akimasa

2018-06-01

Purpose Right-sided aortic arch is a rare vessel anomaly with an incidence of 0.1% worldwide. Supra-aortic branches form a mirror image of the left-sided aortic arch or an aberrant left subclavian artery associated with Kommerell diverticulum. Most patients are diagnosed by a difference in blood pressure in each upper extremity or by the presence of left subclavian steal syndrome in their younger age. The diagnosis of onset of ischemic stroke in middle age is rare. Methods We present the case of a female patient who presented with an ischemic stroke in the left posterior circulation area. She had no history of congenital heart malformation. We performed head magnetic resonance imaging, cerebral angiography, and enhanced computed tomography of the aortic arch and major branches. Results The patient had a right-sided aortic arch and an aberrant left subclavian artery. The left subclavian artery was occluded at the proximal portion with a fibrous string. Collateral flow in the anterior cervical subcutaneous area supported left limb perfusion. Conclusion An atheromatous change reduced shunt flow via collateral networks at the anterior cervical region. Congenital subclavian steal supported the ischemic stroke.

Strain measurement of abdominal aortic aneurysm with real-time 3D ultrasound speckle tracking.

PubMed

Bihari, P; Shelke, A; Nwe, T H; Mularczyk, M; Nelson, K; Schmandra, T; Knez, P; Schmitz-Rixen, T

2013-04-01

Abdominal aortic aneurysm rupture is caused by mechanical vascular tissue failure. Although mechanical properties within the aneurysm vary, currently available ultrasound methods assess only one cross-sectional segment of the aorta. This study aims to establish real-time 3-dimensional (3D) speckle tracking ultrasound to explore local displacement and strain parameters of the whole abdominal aortic aneurysm. Validation was performed on a silicone aneurysm model, perfused in a pulsatile artificial circulatory system. Wall motion of the silicone model was measured simultaneously with a commercial real-time 3D speckle tracking ultrasound system and either with laser-scan micrometry or with video photogrammetry. After validation, 3D ultrasound data were collected from abdominal aortic aneurysms of five patients and displacement and strain parameters were analysed. Displacement parameters measured in vitro by 3D ultrasound and laser scan micrometer or video analysis were significantly correlated at pulse pressures between 40 and 80 mmHg. Strong local differences in displacement and strain were identified within the aortic aneurysms of patients. Local wall strain of the whole abdominal aortic aneurysm can be analysed in vivo with real-time 3D ultrasound speckle tracking imaging, offering the prospect of individual non-invasive rupture risk analysis of abdominal aortic aneurysms. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Late outcome analysis of the Braile Biomédica® pericardial valve in the aortic position

PubMed Central

Azeredo, Lisandro Gonçalves; Veronese, Elinthon Tavares; Santiago, José Augusto Duncan; Brandão, Carlos Manuel de Almeida; Pomerantzeff, Pablo Maria Alberto; Jatene, Fabio Biscegli

2014-01-01

Objective Aortic valve replacement with Braile bovine pericardial prosthesis has been routinely done at the Heart Institute of the Universidade de São Paulo Medical School since 2006. The objective of this study is to analyze the results of Braile Biomédica® aortic bioprosthesis in patients with aortic valve disease. Methods We retrospectively evaluated 196 patients with aortic valve disease submitted to aortic valve replacement with Braile Biomédica® bovine pericardial prosthesis, between 2006 and 2010. Mean age was 59.41±16.34 years and 67.3% were male. Before surgery, 73.4% of patients were in NYHA functional class III or IV. Results Hospital mortality was 8.16% (16 patients). Linearized rates of mortality, endocarditis, reintervention, and structural dysfunction were 1.065%, 0.91%, 0.68% and 0.075% patients/year, respectively. Actuarial survival was 90.59±2.56% in 88 months. Freedom from reintervention, endocarditis and structural dysfunction was respectively 91.38±2.79%, 89.84±2.92% and 98.57±0.72% in 88 months. Conclusion The Braile Biomédica® pericardial aortic valve prosthesis demonstrated actuarial survival and durability similar to that described in the literature, but further follow up is required to assess the incidence of prosthetic valve endocarditis and structural dysfunction in the future. PMID:25372903

Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions.

PubMed

Khanafer, Khalil M; Bull, Joseph L; Upchurch, Gilbert R; Berguer, Ramon

2007-01-01

The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non-Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture.

Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients.

PubMed

Reardon, Michael J; Van Mieghem, Nicolas M; Popma, Jeffrey J; Kleiman, Neal S; Søndergaard, Lars; Mumtaz, Mubashir; Adams, David H; Deeb, G Michael; Maini, Brijeshwar; Gada, Hemal; Chetcuti, Stanley; Gleason, Thomas; Heiser, John; Lange, Rüdiger; Merhi, William; Oh, Jae K; Olsen, Peter S; Piazza, Nicolo; Williams, Mathew; Windecker, Stephan; Yakubov, Steven J; Grube, Eberhard; Makkar, Raj; Lee, Joon S; Conte, John; Vang, Eric; Nguyen, Hang; Chang, Yanping; Mugglin, Andrew S; Serruys, Patrick W J C; Kappetein, Arie P

2017-04-06

Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).

Low-level overexpression of p53 promotes warfarin-induced calcification of porcine aortic valve interstitial cells by activating Slug gene transcription.

PubMed

Gao, Li; Ji, Yue; Lu, Yan; Qiu, Ming; Shen, Yejiao; Wang, Yaqing; Kong, Xiangqing; Shao, Yongfeng; Sheng, Yanhui; Sun, Wei

2018-03-09

The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the slug promoter and activated slug expression in calcific pAVICs. Of note, overexpression of Slug increased osteogenic marker Runx2 expression, but not pAVIC calcium deposition, and Slug knockdown attenuated pAVIC calcification and p53-mediated pAVIC calcium deposition and expression of osteogenic markers. In conclusion, we found that p53 plays an important role in warfarin induced pAVIC calcification, and increased slug transcription by p53 is required for p53-mediated pAVIC calcification. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Noninvasive measurement of regional pulse wave velocity in human ascending aorta with ultrasound imaging: an in-vivo feasibility study.

PubMed

Huang, Chengwu; Guo, Dong; Lan, Feng; Zhang, Hongjia; Luo, Jianwen

2016-10-01

Accurate and noninvasive techniques for measurement of local/regional pulse wave velocity (PWV), instead of global PWV, is desired for quantifying localized arterial stiffness and improving cardiovascular disease assessment. This study aimed at investigating the feasibility of regional PWV measurement in human ascending aorta in vivo using an ultrasound-based technique. Proximal ascending aortas of 76 healthy patients (23-71 years) were scanned with transthoracic echocardiography in parasternal long-axis view, and ultrasound radiofrequency data were acquired in a high temporal resolution (∼404 Hz). The PWV was derived from the determination of arrival times and identification of travel distances. Both PWVs in early systolic phase (PWVsf; pulse wave velocity measured using the systolic foot as characteristic time point) and late systolic phase (PWVdn; pulse wave velocity measured using the dicrotic notch as characteristic time point) were obtained. The PWVsf and PWVdn were 4.58 ± 1.38 and 6.51 ± 1.90 m/s, respectively, and both were correlated with age (r = 0.30, P = 0.02 and r = 0.71, P < 0.0001). The measurements were reproducible, and PWVdn showed significant correlation with aortic diameter (r = 0.53, P < 0.0001), relative distension (r = -0.44, P = 0.0002), and local PWV derived from Bramwell-Hill equation (r = 35, P = 0.004). The PWV difference (PWVdn - PWVsf) reflected aortic stiffness change within cardiac cycle from early systole to late systole and was also correlated with age (r = 0.50, P < 0.0001). The feasibility of ascending aortic PWV measurement using ultrasound imaging was illustrated in vivo, suggesting the potential of the technique in characterization of regional aortic stiffness and assessment of aortic diseases.

Magnetic resonance measurement of turbulent kinetic energy for the estimation of irreversible pressure loss in aortic stenosis.

PubMed

Dyverfeldt, Petter; Hope, Michael D; Tseng, Elaine E; Saloner, David

2013-01-01

The authors sought to measure the turbulent kinetic energy (TKE) in the ascending aorta of patients with aortic stenosis and to assess its relationship to irreversible pressure loss. Irreversible pressure loss caused by energy dissipation in post-stenotic flow is an important determinant of the hemodynamic significance of aortic stenosis. The simplified Bernoulli equation used to estimate pressure gradients often misclassifies the ventricular overload caused by aortic stenosis. The current gold standard for estimation of irreversible pressure loss is catheterization, but this method is rarely used due to its invasiveness. Post-stenotic pressure loss is largely caused by dissipation of turbulent kinetic energy into heat. Recent developments in magnetic resonance flow imaging permit noninvasive estimation of TKE. The study was approved by the local ethics review board and all subjects gave written informed consent. Three-dimensional cine magnetic resonance flow imaging was used to measure TKE in 18 subjects (4 normal volunteers, 14 patients with aortic stenosis with and without dilation). For each subject, the peak total TKE in the ascending aorta was compared with a pressure loss index. The pressure loss index was based on a previously validated theory relating pressure loss to measures obtainable by echocardiography. The total TKE did not appear to be related to global flow patterns visualized based on magnetic resonance-measured velocity fields. The TKE was significantly higher in patients with aortic stenosis than in normal volunteers (p < 0.001). The peak total TKE in the ascending aorta was strongly correlated to index pressure loss (R(2) = 0.91). Peak total TKE in the ascending aorta correlated strongly with irreversible pressure loss estimated by a well-established method. Direct measurement of TKE by magnetic resonance flow imaging may, with further validation, be used to estimate irreversible pressure loss in aortic stenosis. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Aortic Curvature Instead of Angulation Allows Improved Estimation of the True Aorto-iliac Trajectory.

PubMed

Schuurmann, R C L; Kuster, L; Slump, C H; Vahl, A; van den Heuvel, D A F; Ouriel, K; de Vries, J-P P M

2016-02-01

Supra- and infrarenal aortic neck angulation have been associated with complications after endovascular aortic aneurysm repair. However, a uniform angulation measurement method is lacking and the concept of angulation suggests a triangular oversimplification of the aortic anatomy. (Semi-)automated calculation of curvature along the center luminal line describes the actual trajectory of the aorta. This study proposes a methodology for calculating aortic (neck) curvature and suggests an additional method based on available tools in current workstations: curvature by digital calipers (CDC). Proprietary custom software was developed for automatic calculation of the severity and location of the largest supra- and infrarenal curvature over the center luminal line. Twenty-four patients with severe supra- or infrarenal angulations (≥45°) and 11 patients with small to moderate angulations (<45°) were included. Both CDC and angulation were measured by two independent observers on the pre- and postoperative computed tomographic angiography scans. The relationships between actual curvature and CDC and angulation were visualized and tested with Pearson's correlation coefficient. The CDC was also fully automatically calculated with proprietary custom software. The difference between manual and automatic determination of CDC was tested with a paired Student t test. A p-value was considered significant when two-tailed α < .05. The correlation between actual curvature and manual CDC is strong (.586-.962) and even stronger for automatic CDC (.865-.961). The correlation between actual curvature and angulation is much lower (.410-.737). Flow direction angulation values overestimate CDC measurements by 60%, with larger variance. No significant difference was found in automatically calculated CDC values and manually measured CDC values. Curvature calculation of the aortic neck improves determination of the true aortic trajectory. Automatic calculation of the actual curvature is preferable, but measurement or calculation of the curvature by digital calipers is a valid alternative if actual curvature is not at hand. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

PubMed

Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

2016-02-01

Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

Combined Open and Endovascular Repair for Aortic Arch Pathology

PubMed Central

Kang, Woong Chol; Ahn, Tae Hoon; Lee, Kyung Hoon; Moon, Chan Il; Han, Seung Hwan; Park, Chul-Hyun; Park, Kook-Yang; Kang, Jin Mo; Kim, Jung Ho

2010-01-01

Background and Objectives We describe our experience with combined open and endovascular repair in patients who have aortic arch pathology. Subjects and Methods This study is a retrospective analysis of 7 patients who underwent combined open and endovascular repair for aortic arch pathology. Medical records and radiographic information were reviewed. Results A total of 7 consecutive patients (5 men, 71.4%) underwent thoracic stent graft implantation. The mean age was 59.9±16.7 years. The indication for endovascular repair was aneurysmal degeneration in 5 patients, and rupture or impending rupture in 2 patients. In all 7 cases, supra-aortic transposition of the great vessels was performed successfully. Stent graft implantation was achieved in all cases. Surgical exposure of the access vessel was necessary in 2 patients. A total of 9 stent grafts were implanted (3 stent grafts in one patient). The Seal thoracic and the Valiant endovascular stent graft were implanted in 6 patients and 1 patient, respectively. There were no post-procedure deaths or neurologic complications. In 2 patients, bleeding and injury of access vessel were noted after the procedure. Postoperative endoleak was noted in 1 patient. One patient died at 10 months after the procedure due to a newly developed ascending aortic dissection. No patients required secondary intervention during the follow-up period. The aortic diameter decreased in 4 patients. In 3 patients, including 1 patient with endoleak, there was no change in aortic diameter. Conclusion Our experience suggests that combined open and endovascular repair for aortic arch pathology is safe and effective, with few complications. PMID:20830254

Cryopreserved Human Allografts for the Reconstruction of Aortic and Peripheral Prosthetic Graft Infection.

PubMed

Bossi, Matteo; Tozzi, Matteo; Franchin, Marco; Ferraro, Stefania; Rivolta, Nicola; Ferrario, Massimo; Guttadauro, Chiara; Castelli, Patrizio; Piffaretti, Gabriele

2017-12-25

Background : This study aimed to present cases with cryopreserved human allografts (CHAs) for vascular reconstruction in both aortic and peripheral infected prosthetic grafts. Materials and Methods : This is a single center, observational descriptive study with retrospective analysis. In all cases, the infected prosthetic graft material was completely removed. At discharge, patients were administered anticoagulants. Follow-up examinations included clinical visits, echo-color-Doppler ultrasounds, or computed tomography angiography within 30 days and at 3, 6, and 12 months after the treatment, and then twice per year. Results : We treated 21 patients (90% men, n=19) with the mean age of 71±12 years and mean interval between the initial operation and replacement with CHA of 30 months [range, 1-216; interquartile range (IQR), 2-36]. In-hospital mortality was 14% (n=3); no CHA-related complication led to death. Limb salvage was 100%. No patient was lost at the median follow-up of 14 months (range, 2-61; IQR, 6-39). No rupture, aneurysmal degeneration, or re-infection occurred. Estimated freedom from CHA-related adverse events (95% confidence interval, 43-63) was 95% at 3 years. Conclusion : In our experience, CHAs are a viable option for prosthetic graft infections and provide satisfactory clinical results and favorable stability because of a very low rate of CHA-related adverse events during follow-up.

Response of the Cardiovascular System to Vibration and Combined Stresses

DTIC Science & Technology

1975-08-31

Canines were chronically instrumented for continuous measurements of ascending aortic flow ( Zepeda ), left ventricular pressure (Konigsberg), circum- flex...different animals. Each dog was chronically instrumented for continuous measuremernt of ascending aortic flow ( Zepeda ), left ventricular pressure...vibration protocol as those animals restrained vertically. METHODS Canines (16 to 22 kg) were chronically instrumented with electromagnetic flow cuffs ( Zepeda

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model

PubMed Central

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Introduction: Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Methods: Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Results: Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma brain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10–0.12) with the mid- and high-dose carvedilol treatment. Conclusion: A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model. PMID:28491305

Biomechanical properties of the thoracic aorta in Marfan patients

PubMed Central

Sulejmani, Fatiesa; Pokutta-Paskaleva, Anastassia; Ziganshin, Bulat; Leshnower, Bradley; Iannucci, Glen; Elefteriades, John

2017-01-01

Background Marfan syndrome (MFS), a genetic disorder of the connective tissue, has been strongly linked to dilation of the thoracic aorta, among other cardiovascular complications. As a result, MFS patients frequently suffer from aortic dissection and rupture, contributing to the high rate of mortality and morbidity among MFS patients. Despite the significant effort devoted to the investigation of mechanical and structural properties of aneurysmal tissue, studies on Marfan aneurysmal biomechanics are scarce. Ex vivo mechanical characterization of MFS aneurysmal tissue can provide a better insight into tissue strength outside the physiologic loading range and serve as a basis for improved risk assessment and failure prediction. Methods The mechanical and microstructural properties of MFS aneurysmal thoracic aorta (MFS, n=15, 39.5±3.91 years), non-MFS aneurysmal thoracic aorta (TAA, n=8, 52.8±4.9 years), healthy human thoracic aorta (HH, n=8, 75.4±6.1 years), and porcine thoracic aorta (n=10) are investigated. Planar biaxial tensile testing and uniaxial failure testing were utilized to characterize the mechanical and failure properties of the tissue, respectively. Verhoeff-Van Gieson (VVG) and PicroSirius Red stains were utilized to visualize the elastin and collagen fiber architecture, respectively. Results MFS tissue was found to have age-dependent but diameter-independent mechanical, structural, and morphological properties, also showing extensive elastin fiber degradation. Non-MFS thoracic aneurysmal aorta was thicker and stiffer than age-matched MFS tissue. Moreover, non-MFS thoracic aneurysmal mechanics resembled closely the mechanics of older healthy human tissue. Younger MFS tissue (<40 years) exhibited similar mechanical and structural properties to aged porcine tissue. Conclusions Both age and aneurysmal presence were found to be factors associated with increased stiffness in aortic tissue, and aortic diameter was not a significant determinant of mechanical property deterioration. Additionally, the presence of MFS was found to induce stiffening of the thoracic aorta, although not to the extent of the non-MFS aneurysm. PMID:29270373

Automated measurement of uptake in cerebellum, liver, and aortic arch in full-body FDG PET/CT scans.

PubMed

Bauer, Christian; Sun, Shanhui; Sun, Wenqing; Otis, Justin; Wallace, Audrey; Smith, Brian J; Sunderland, John J; Graham, Michael M; Sonka, Milan; Buatti, John M; Beichel, Reinhard R

2012-06-01

The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control. Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard. For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch. With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials. © 2012 American Association of Physicists in Medicine.

Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans

PubMed Central

Graham, Mark J.; Viney, Nick; Crooke, Rosanne M.; Tsimikas, Sotirios

2016-01-01

Epidemiological, genetic association, and Mendelian randomization studies have provided strong evidence that lipoprotein (a) [Lp(a)] is an independent causal risk factor for CVD, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. Lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with CVD and aortic stenosis. These data support the notion that Lp(a) should be a target of therapy for CVD event reduction and to reduce progression of aortic stenosis. However, effective therapies to specifically reduce plasma Lp(a) levels are lacking. Recent animal and human studies have shown that Lp(a) can be specifically targeted with second generation antisense oligonucleotides (ASOs) that inhibit apo(a) mRNA translation. In apo(a) transgenic mice, an apo(a) ASO reduced plasma apo(a)/Lp(a) levels and their associated oxidized phospholipid (OxPL) levels by 86 and 93%, respectively. In cynomolgus monkeys, a second generation apo(a) ASO, ISIS-APO(a)Rx, significantly reduced hepatic apo(a) mRNA expression and plasma Lp(a) levels by >80%. Finally, in a phase I study in normal volunteers, ISIS-APO(a)Rx ASO reduced Lp(a) levels and their associated OxPL levels up to 89 and 93%, respectively, with minimal effects on other lipoproteins. ISIS-APO(a)Rx represents the first specific and potent drug in clinical development to lower Lp(a) levels and may be beneficial in reducing CVD events and progression of calcific aortic valve stenosis. PMID:26538546

Nitric Oxide Stimulates Matrix Synthesis and Deposition by Adult Human Aortic Smooth Muscle Cells Within Three-Dimensional Cocultures

PubMed Central

Simmers, Phillip; Gishto, Arsela; Vyavahare, Narendra

2015-01-01

Vascular diseases are characterized by the over-proliferation and migration of aortic smooth muscle cells (SMCs), and degradation of extracellular matrix (ECM) within the vessel wall, leading to compromise in cell–cell and cell–matrix signaling pathways. Tissue engineering approaches to regulate SMC over-proliferation and enhance healthy ECM synthesis showed promise, but resulted in low crosslinking efficiency. Here, we report the benefits of exogenous nitric oxide (NO) cues, delivered from S-Nitrosoglutathione (GSNO), to cell proliferation and matrix deposition by adult human aortic SMCs (HA-SMCs) within three-dimensional (3D) biomimetic cocultures. A coculture platform with two adjacent, permeable 3D culture chambers was developed to enable paracrine signaling between vascular cells. HA-SMCs were cultured in these chambers within collagen hydrogels, either alone or in the presence of human aortic endothelial cells (HA-ECs) cocultures, and exogenously supplemented with varying GSNO dosages (0–100 nM) for 21 days. Results showed that EC cocultures stimulated SMC proliferation within GSNO-free cultures. With increasing GSNO concentration, HA-SMC proliferation decreased in the presence or absence of EC cocultures, while HA-EC proliferation increased. GSNO (100 nM) significantly enhanced the protein amounts synthesized by HA-SMCs, in the presence or absence of EC cocultures, while lower dosages (1–10 nM) offered marginal benefits. Multi-fold increases in the synthesis and deposition of elastin, glycosaminoglycans, hyaluronic acid, and lysyl oxidase crosslinking enzyme (LOX) were noted at higher GSNO dosages, and coculturing with ECs significantly furthered these trends. Similar increases in TIMP-1 and MMP-9 levels were noted within cocultures with increasing GSNO dosages. Such increases in matrix synthesis correlated with NO-stimulated increases in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression within EC and SMC cultures, respectively. Results attest to the benefits of delivering NO cues to suppress SMC proliferation and promote robust ECM synthesis and deposition by adult human SMCs, with significant applications in tissue engineering, biomaterial scaffold development, and drug delivery. PMID:25597545

The Burden of Hard Atherosclerotic Plaques Does Not Promote Endoleak Development After Endovascular Aortic Aneurysm Repair: A Risk Stratification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, Johannes, E-mail: johannes.petersen@i-med.ac.at; Glodny, Bernhard, E-mail: bernhard.glodny@i-med.ac.at

Purpose: To objectify the influence of the atherosclerotic burden in the proximal landing zone on the development of endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) or thoracic endovascular aneurysm repair (TEVAR) using objective aortic calcium scoring (ACS). Materials and Methods: This retrospective observation study included 267 patients who received an aortic endograft between 1997 and 2010 and for whom preoperative computed tomography (CT) was available to perform ACS using the CT-based V600 method. The mean follow-up period was 2 {+-} 2.3 years. Results: Type I endoleaks persisted in 45 patients (16.9%), type II in 34 (12.7%), type III inmore » 8 (3%), and type IV or V in 3 patients, respectively (1.1% each). ACS in patients with type I endoleaks was not increased: 0.029 {+-} 0.061 ml compared with 0.075 {+-} 0.1349 ml in the rest of the patients, (p > 0.05; Whitney-Mann U-Test). There were significantly better results for the indication 'traumatic aortic rupture' than for the other indications (p < 0.05). In multivariate logistic regression analyses, age was an independent risk factor for the development of type I endoleaks in the thoracic aorta (Wald 9.5; p = 0.002), whereas ACS score was an independent protective factor (Wald 6.9; p = 0.009). In the abdominal aorta, neither age nor ACS influenced the development of endoleaks. Conclusion: Contrary to previous assumptions, TEVAR and EVAR can be carried out without increasing the risk of an endoleak of any type, even if there is a high atherosclerotic 'hard-plaque' burden of the aorta. The results are significantly better for traumatic aortic.« less

Influence of renal artery variants, number, location, and degree of renal artery stenoses on the atherosclerotic burden of the aorta.

PubMed

Petersen, Johannes; Plaikner, Michaela; Nasseri, Parinaz; Rehder, Peter; Koppelstätter, Christian; Pauli, Guido F; Glodny, Bernhard

2012-10-01

To determine the assumed influence of the number of renal arteries, the distribution and extent of renal artery stenosis (RAS), and the kidney length on calcified aortic atherosclerotic plaque burden. The computed tomographic angiographies of 1381 patients were analyzed retrospectively using a volumetric aortic calcium scoring method. The Spearman method was used to calculate the correlation between kidney length, number and diameter of renal arteries, as well as number, degree, and location of RASs on main or additional renal arteries with the extent of aortic atherosclerosis. Logistic regression analyses were conducted with the target variable "calcification present or absent." Patients with multiple renal arteries (38.3%) had lower plaque volumes than patients without such variants (0.55 ± 0.97 vs 0.64 ± 1.06 mL; P < 0.05). Renal artery stenoses affected all renal vessels with equal frequency. The aortic calcium score correlated with the number of RASs (P < 0.0001) and the maximum degree of RAS up to a threshold of 60%. Location of an RAS in the various renal arteries was irrelevant. In regression analyses, the presence of RAS (Wald = 5.523), the degree of RAS (Wald = 6.251), and age (Wald = 223.1) were positive predictors of the aortic calcium score, whereas kidney length (Wald = 9.564) proved to be a negative predictor. The aortic calcium score correlates with both the number of RASs and the maximum degree of RAS up to a threshold of 60% but correlates inversely with the number of renal arteries. Renal artery stenosis affects all renal vessels with equal frequency, and this finding should be considered in screening procedures.

Intravenously injected human multilineage-differentiating stress-enduring cells selectively engraft into mouse aortic aneurysms and attenuate dilatation by differentiating into multiple cell types.

PubMed

Hosoyama, Katsuhiro; Wakao, Shohei; Kushida, Yoshihiro; Ogura, Fumitaka; Maeda, Kay; Adachi, Osamu; Kawamoto, Shunsuke; Dezawa, Mari; Saiki, Yoshikatsu

2018-06-01

Aortic aneurysms result from the degradation of multiple components represented by endothelial cells, vascular smooth muscle cells, and elastic fibers. Cells that can replenish these components are desirable for cell-based therapy. Intravenously injected multilineage-differentiating stress-enduring (Muse) cells, endogenous nontumorigenic pluripotent-like stem cells, reportedly integrate into the damaged site and repair the tissue through spontaneous differentiation into tissue-compatible cells. We evaluated the therapeutic efficacy of Muse cells in a murine aortic aneurysm model. Human bone marrow Muse cells, isolated as stage-specific embryonic antigen-3 + from bone marrow mesenchymal stem cells, or non-Muse cells (stage-specific embryonic antigen-3 - cells in mesenchymal stem cells), bone marrow mesenchymal stem cells, or vehicle was intravenously injected at day 0, day 7, and 2 weeks (20,000 cells/injection) after inducing aortic aneurysms by periaortic incubation of CaCl 2 and elastase in severe combined immunodeficient mice. At 8 weeks, infusion of human Muse cells attenuated aneurysm dilation, and the aneurysmal size in the Muse group corresponded to approximately 62.5%, 55.6%, and 45.6% in the non-Muse, mesenchymal stem cell, and vehicle groups, respectively. Multiphoton laser confocal microscopy revealed that infused Muse cells migrated into aneurysmal tissue from the adventitial side and penetrated toward the luminal side. Histologic analysis demonstrated robust preservation of elastic fibers and spontaneous differentiation into endothelial cells and vascular smooth muscle cells. After intravenous injection, Muse cells homed and expanded to the aneurysm from the adventitial side. Subsequently, Muse cells differentiated spontaneously into vascular smooth muscle cells and endothelial cells, and elastic fibers were preserved. These Muse cell features together led to substantial attenuation of aneurysmal dilation. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report

PubMed Central

HWANG, HUI-JEONG; YOON, KYUNG LIM; SOHN, IL SUK

2016-01-01

The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans. PMID:26998021

Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report.

PubMed

Hwang, Hui-Jeong; Yoon, Kyung Lim; Sohn, Il Suk

2016-03-01

The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans.

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

PubMed

Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

2018-03-08

Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007). Circumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Hybrid treatment of aortic arch disease

PubMed Central

Metzger, Patrick Bastos; Rossi, Fabio Henrique; Moreira, Samuel Martins; Issa, Mario; Izukawa, Nilo Mitsuru; Dinkhuysen, Jarbas J.; Spina Neto, Domingos; Kambara, Antônio Massamitsu

2014-01-01

Introduction The management of thoracic aortic disease involving the ascending aorta, aortic arch and descending thoracic aorta are technically challenging and is an area in constant development and innovation. Objective To analyze early and midterm results of hybrid treatment of arch aortic disease. Methods Retrospective study of procedures performed from January 2010 to December 2012. The end points were the technical success, therapeutic success, morbidity and mortality, neurologic outcomes, the rate of endoleaks and reinterventions. Results A total of 95 patients treated for thoracic aortic diseases in this period, 18 underwent hybrid treatment and entered in this study. The average ages were 62.3 years. The male was present in 66.7%. The technical and therapeutic success was 94.5% e 83.3%. The perioperative mortality rate of 11.1%. There is any death during one-year follow- up. The reoperation rates were 16.6% due 2 cases of endoleak Ia and one case of endoleak II. There is any occlusion of anatomic or extra anatomic bypass during follow up. Conclusion In our study, the hybrid treatment of aortic arch disease proved to be a feasible alternative of conventional surgery. The therapeutic success rates and re- interventions obtained demonstrate the necessity of thorough clinical follow-up of these patients in a long time. PMID:25714205

Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics (CFD): presentation of a patient-specific method combining magnetic resonance imaging and numerical simulations.

PubMed

Midulla, Marco; Moreno, Ramiro; Baali, Adil; Chau, Ming; Negre-Salvayre, Anne; Nicoud, Franck; Pruvo, Jean-Pierre; Haulon, Stephan; Rousseau, Hervé

2012-10-01

In the last decade, there was been increasing interest in finding imaging techniques able to provide a functional vascular imaging of the thoracic aorta. The purpose of this paper is to present an imaging method combining magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain a patient-specific haemodynamic analysis of patients treated by thoracic endovascular aortic repair (TEVAR). MRI was used to obtain boundary conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences which covered the whole thoracic aorta. Phase contrast imaging provided the inlet and outlet profiles. A CFD mesh generator was used to model the arterial morphology, and wall movements were imposed according to the cine imaging. CFD runs were processed using the finite volume (FV) method assuming blood as a homogeneous Newtonian fluid. Twenty patients (14 men; mean age 62.2 years) with different aortic lesions were evaluated. Four-dimensional mapping of velocity and wall shear stress were obtained, depicting different patterns of flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress in-stent and along the native aorta. A computational method using a combined approach with MRI appears feasible and seems promising to provide detailed functional analysis of thoracic aorta after stent-graft implantation. • Functional vascular imaging of the thoracic aorta offers new diagnostic opportunities • CFD can model vascular haemodynamics for clinical aortic problems • Combining CFD with MRI offers patient specific method of aortic analysis • Haemodynamic analysis of stent-grafts could improve clinical management and follow-up.

Standardized 2D ultrasound versus 3D/4D ultrasound and image fusion for measurement of aortic aneurysm diameter in follow-up after EVAR.

PubMed

Pfister, Karin; Schierling, Wilma; Jung, Ernst Michael; Apfelbeck, Hanna; Hennersperger, Christoph; Kasprzak, Piotr M

2016-01-01

To compare standardised 2D ultrasound (US) to the novel ultrasonographic imaging techniques 3D/4D US and image fusion (combined real-time display of B mode and CT scan) for routine measurement of aortic diameter in follow-up after endovascular aortic aneurysm repair (EVAR). 300 measurements were performed on 20 patients after EVAR by one experienced sonographer (3rd degree of the German society of ultrasound (DEGUM)) with a high-end ultrasound machine and a convex probe (1-5 MHz). An internally standardized scanning protocol of the aortic aneurysm diameter in B mode used a so called leading-edge method. In summary, five different US methods (2D, 3D free-hand, magnetic field tracked 3D - Curefab™, 4D volume sweep, image fusion), each including contrast-enhanced ultrasound (CEUS), were used for measurement of the maximum aortic aneurysm diameter. Standardized 2D sonography was the defined reference standard for statistical analysis. CEUS was used for endoleak detection. Technical success was 100%. In augmented transverse imaging the mean aortic anteroposterior (AP) diameter was 4.0±1.3 cm for 2D US, 4.0±1.2 cm for 3D Curefab™, and 3.9±1.3 cm for 4D US and 4.0±1.2 for image fusion. The mean differences were below 1 mm (0.2-0.9 mm). Concerning estimation of aneurysm growth, agreement was found between 2D, 3D and 4D US in 19 of the 20 patients (95%). Definitive decision could always be made by image fusion. CEUS was combined with all methods and detected two out of the 20 patients (10%) with an endoleak type II. In one case, endoleak feeding arteries remained unclear with 2D CEUS but could be clearly localized by 3D CEUS and image fusion. Standardized 2D US allows adequate routine follow-up of maximum aortic aneurysm diameter after EVAR. Image Fusion enables a definitive statement about aneurysm growth without the need for new CT imaging by combining the postoperative CT scan with real-time B mode in a dual image display. 3D/4D CEUS and image fusion can improve endoleak characterization in selected cases but are not mandatory for routine practice.

The German Aortic Valve Registry (GARY): in-hospital outcome

PubMed Central

Hamm, Christian W.; Möllmann, Helge; Holzhey, David; Beckmann, Andreas; Veit, Christof; Figulla, Hans-Reiner; Cremer, J.; Kuck, Karl-Heinz; Lange, Rüdiger; Zahn, Ralf; Sack, Stefan; Schuler, Gerhard; Walther, Thomas; Beyersdorf, Friedhelm; Böhm, Michael; Heusch, Gerd; Funkat, Anne-Kathrin; Meinertz, Thomas; Neumann, Till; Papoutsis, Konstantinos; Schneider, Steffen; Welz, Armin; Mohr, Friedrich W.

2014-01-01

Background Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis. Methods and results A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI). Conclusion The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients. PMID:24022003

[Late reoperations after repaired Stanford type A aortic dissection].

PubMed

Huang, F H; Li, L P; Su, C H; Qin, W; Xu, M; Wang, L M; Jiang, Y S; Qiu, Z B; Xiao, L Q; Zhang, C; Shi, H W; Chen, X

2017-04-01

Objective: To summarize the experience of reoperations on patients who had late complications related to previous aortic surgery for Stanford type A dissection. Methods: From August 2008 to October 2016, 14 patients (10 male and 4 female patients) who underwent previous cardiac surgery for Stanford type A aortic dissection accepted reoperations on the late complications at Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University. The range of age was from 41 to 76 years, the mean age was (57±12) years. In these patients, first time operations were ascending aorta replacement procedure in 3 patients, ascending aorta combined with partial aortic arch replacement in 4 patients, aortic root replacement (Bentall) associated with Marfan syndrome in 3 patients, aortic valve combined with ascending aorta replacement (Wheat) in 1 patient, ascending aorta combined with Sun's procedure in 1 patient, Wheat combined with Sun's procedure in 1 patient, Bentall combined with Sun's procedure in 1 patient. The interval between two operations averaged 0.3 to 10.0 years with a mean of (4.8±3.1) years. The reasons for reoperations included part anastomotic split, aortic valve insufficiency, false aneurysm formation, enlargement of remant aortal and false cavity. The selection of reoperation included anastomotic repair, aortic valve replacement, total arch replacement and Sun's procedure. Results: Of the 14 patients, the cardiopulmonary bypass times were 107 to 409 minutes with a mean of (204±51) minutes, cross clamp times were 60 to 212 minutes with a mean of (108±35) minutes, selective cerebral perfusion times were 16 to 38 minutes with a mean of (21±11) minutes. All patients survived from the operation, one patient died from severe pulmonary infection 50 days after operation. Three patients had postoperative complications, including acute renal failure of 2 patients and pulmonary infection of 1 patient, and these patients were recovered after treatment. Thirteen patients were finally recovered from hospital. The patients were followed up for 16 to 45 months, and no aortic rupture, paraplegia and death were observed in the follow-up. Conclusions: Patients for residual aortic dissection after initial operations on Stanford type A aortic dissection should be attached great importance and always need emergency surgery, but the technique is demanding and risk is great for surgeons and patients, which need enough specification and accurate on aortic operation. More importantly, the Sun's procedure also should be performed on the treatment of residual aortic dissection or distal arch expansion, and obtains the short- and long-term results in the future.

A Protocol for Diagnosis and Management of Aortic Atherosclerosis in Cardiac Surgery Patients

PubMed Central

Brandon Bravo Bruinsma, George J.; Van 't Hof, Arnoud W. J.; Grandjean, Jan G.; Nierich, Arno P.

2017-01-01

In patients undergoing cardiac surgery, use of perioperative screening for aortic atherosclerosis with modified TEE (A-View method) was associated with lower postoperative mortality, but not stroke, as compared to patients operated on without such screening. At the time of clinical implementation and validation, we did not yet standardize the indications for modified TEE and the changes in patient management in the presence of aortic atherosclerosis. Therefore, we designed a protocol, which combined the diagnosis of atherosclerosis of thoracic aorta and the subsequent considerations with respect to the intraoperative management and provides a systematic approach to reduce the risk of cerebral complications. PMID:28852575

Abdominal Aortic Aneurysm: Novel Mechanisms and Therapies

PubMed Central

Davis, Frank M.; Rateri, Debra L.; Daugherty, Alan

2015-01-01

Purpose of review Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. Recent Findings An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, MMP3, TGFβR2 and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Recent preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight for roles of microRNAs to regulate many pathological pathways in AAA development. Several large clinical trials are ongoing seeking to translate preclinical findings into therapeutic options. Summary Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight for the development of a medical treatment for this disease. PMID:26352243

Sex differences in abdominal aortic aneurysms.

PubMed

Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H

2018-06-01

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ClinicalTrials.gov

2018-02-19

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

Surgical treatment of middle aortic syndrome with Takayasu arteritis or midaortic dysplastic syndrome.

PubMed

Kim, S M; Jung, I M; Han, A; Min, S-I; Lee, T; Ha, J; Kim, S J; Min, S-K

2015-08-01

Middle aortic syndrome (MAS) is a rare condition characterized by severe stenosis of the distal thoracic or abdominal aorta. The aims of this study are to define the anatomic characteristics of MAS and to review the various surgical methods and their outcomes in terms of long-term durability Ten adult patients were diagnosed with MAS caused by Takayasu arteritis (TA) or midaortic dysplastic syndrome and underwent surgical treatment between July 1992 and January 2013. The aortic lesions were mostly suprarenal (n = 7) and stenoses were commonly found in the celiac axis (n = 6), SMA (n = 7), and renal artery (n = 6). Indications for operation were uncontrolled hypertension in six patients and lower extremity claudication in four. Eight aortic bypasses, one supraceliac aortic interposition graft, and one bilateral aorto-renal bypass were performed. Adjunctive renal bypass with saphenous vein graft (n = 4) and IMA reimplantation (n = 2) were performed simultaneously. There was no post-operative mortality, and one complication of iliac dissection at the distal anastomosis site was detected and treated by stenting. Hypertension was cured or improved in five of the six patients, and lower extremity claudication improved in all of them. With a median follow up of 60 months (range, 12-263), all the aortic bypasses were patent and one adjunctive renal artery bypass graft with aortic bypass was occluded 29 months post-operatively. Aortic bypass for MAS is safe and shows excellent long-term durability. Considering the patients are relatively young with a long life expectancy, aggressive surgical treatment could be beneficial. Lifelong follow up to monitor complications and disease progression is necessary. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Balloon aortic valvuloplasty as a bridge-to-decision in high risk patients with aortic stenosis: a new paradigm for the heart team decision making

PubMed Central

Saia, Francesco; Moretti, Carolina; Dall'Ara, Gianni; Ciuca, Cristina; Taglieri, Nevio; Berardini, Alessandra; Gallo, Pamela; Cannizzo, Marina; Chiarabelli, Matteo; Ramponi, Niccolò; Taffani, Linda; Bacchi-Reggiani, Maria Letizia; Marrozzini, Cinzia; Rapezzi, Claudio; Marzocchi, Antonio

2016-01-01

Background Whilst the majority of the patients with severe aortic stenosis can be directly addressed to surgical aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI), in some instances additional information may be needed to complete the diagnostic workout. We evaluated the role of balloon aortic valvuloplasty (BAV) as a bridge-to-decision (BTD) in selected high-risk patients. Methods Between 2007 and 2012, the heart team in our Institution required BTD BAV in 202 patients. Very low left ventricular ejection fraction, mitral regurgitation grade ≥ 3, frailty, hemodynamic instability, serious comorbidity, or a combination of these factors were the main drivers for this strategy. We evaluated how BAV influenced the final treatment strategy in the whole patient group and in each specific subgroup. Results Mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 23.5% ± 15.3%, age 81 ± 7 years. In-hospital mortality was 4.5%, cerebrovascular accident 1% and overall vascular complications 4% (0.5% major; 3.5% minor). Of the 193 patients with BTD BAV who survived and received a second heart team evaluation, 72.6% were finally deemed eligible for definitive treatment (25.4% for AVR; 47.2% for TAVI): 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented serious comorbidities. Conclusions Balloon aortic valvuloplasty can be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive transcatheter or surgical treatment. PMID:27582761

Serum Neutrophil Gelatinase-Associated Lipocalin Levels and Aortic Stiffness in Noncritical Coronary Artery Disease

PubMed Central

Soylu, Korhan; Nar, Gökay; Aksan, Gökhan; Gedikli, Ömer; İnci, Sinan; Yuksel, Serkan; Nar, Rukiye; İdil Soylu, Ayşegül; Gulel, Okan; Şahin, Mahmut

2014-01-01

Aim The aim of this study was to establish the degree of aortic stiffness and levels of neutrophil gelatinase-associated lipocalin (NGAL) in patients with stable ischemic heart disease. Materials and Methods Patients who were found to have stable, noncritical lesions on coronary angiography were included in the study [noncritical coronary artery disease (CAD)]. The control group consisted of those patients who had similar risk profiles and metabolic parameters without atherosclerosis on angiography. Results A total of 101 patients were included in the study of which 56 had noncritical CAD. Whereas the aortic strain (9.11 ± 3.4 vs. 14.01 ± 4.1%, p < 0.001) and aortic distensibility (3.98 ± 1.9 10−6 cm2/dyn vs. 6.33 ± 2.3 10−6 cm2/dyn, p < 0.001) were lower in the noncritical CAD group, the aortic stiffness index was higher (6.34 ± 3.9 vs. 3.37 ± 2.4, p < 0.001) as compared to controls. Serum NGAL levels were higher in the noncritical CAD group (79.29 ± 38.8 vs. 48.05 ± 21.4 ng/ml, p < 0.001). NGAL levels were negatively correlated with aortic strain (p < 0.01, r = 0.57) and distensibility (p < 0.001, r = 0.62), but positively correlated with the aortic stiffness index (p < 0.001, r = 0.72). Conclusion We show that in patients with noncritical CAD, the degree of aortic stiffness and NGAL levels are higher. These markers can be used as tools for further risk stratification of patients with noncritical CAD. PMID:25737678

Possible extracardiac predictors of aortic dissection in Marfan syndrome

PubMed Central

2014-01-01

Background According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. Methods A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-β (TGF-β) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and −9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. Results Among patients with aortic dissection, TGF-β serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. Conclusions We found three easily measurable parameters (striae atrophicae, TGF-β serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR. PMID:24720641

Association of statins with aortic, peripheral, and visceral artery aneurysm development.

PubMed

Mansi, Ishak A; Frei, Christopher R; Halm, Ethan A; Mortensen, Eric M

2017-08-01

Objectives Prior studies examining the effects of statins on arterial aneurysm development and progression yielded conflicting results due to their smaller size and presence of residual confounders. The objective of this study is to examine the association of statins with risk of being diagnosed with aortic, peripheral, and visceral artery aneurysm. Methods This was a retrospective cohort study of Tricare enrollees (from 1 October 2003 to 31 March 2012). Main outcomes were diagnosis of aortic, peripheral, or visceral artery aneurysm and undergoing aortic aneurysm repair procedure during follow-up period. Using 115 baseline characteristics, we generated a propensity score to match statin users and nonusers and examine the odds of outcomes (primary analysis). Secondary analysis examined outcomes at various subcohorts. Results Out of 10,910 statin users and 49,545 nonusers, we propensity score-matched 6728 pairs of statin users and nonusers. Statin users and nonusers had similar odds of being diagnosed with aortic, peripheral, and visceral artery aneurysms (odds ratio [OR]: 1.06, 95% confidence interval [95% CI]: 0.85-1.33) and of undergoing aortic aneurysm repair procedures (OR: 0.54, 95% CI: 0.22-1.35). Secondary analysis showed a tendency toward fewer aortic aneurysm procedures among statin users that did not reach statistical significance. However, high-intensity statin users in comparison to non-intensive statin users had higher adjusted odds of aortic, peripheral, and visceral artery aneurysms (OR: 1.76, 95% CI: 1.37-2.25, p < .0001). Conclusions This study does not support a clinically significant benefit or harm from statins regarding development of arterial aneurysm. However, secondary analyses may support the hypothesis proposed by previous research proposing a bidirectional role for statins.

Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

PubMed

Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A

2016-11-01

Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.

Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

PubMed

An, Zhao; Qiao, Fan; Lu, Qijue; Ma, Ye; Liu, Yang; Lu, Fanglin; Xu, Zhiyun

2017-12-01

Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up-regulation. ATG4B knockdown blocked IL-6-induced autophagy and α-SMA and SM22α degradation, while ATG4B overexpression partly replaced the function of IL-6 in human VSMCs. In conclusion, our study demonstrated that IL-6 downregulated expression of VSMCs contractile proteins α-SMA and SM22α via enhancing ATG4B-mediated autophagy in TAD.

Brain activity monitoring by compressed spectral array during deep hypothermic circulatory arrest in acute aortic dissection surgery.

PubMed

Urbanowicz, Tomasz K; Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek

2014-12-01

Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA.

Battle of the Bulge: Aortic Aneurysm Management From Early Modernity to the Present.

PubMed

Barr, Justin

2017-02-21

For centuries, physicians have recognized aortic aneurysms as an acute threat to life. Therapeutic approaches to the disease began in the 18th century when leading physicians, such as René Laennec and Antonio Valsalva, applied research on circulation and blood coagulation to devise whole-body fasting and bleeding regimens to prevent rupture. After John Hunter's success in ligating arteries to treat peripheral aneurysms, surgeons attempted analogous operations on the aorta, but even the renowned Sir Astley Cooper and William Halsted met with disastrous results. Other clinicians tried various methods of creating intraluminal clots, including the application of such new technologies as electricity and plastic. Vessel repair techniques, pioneered by Alexis Carrel and others in the 20th century, eventually provided a reliably effective treatment. In the past few decades, minimally invasive methods that approach aneurysms endovascularly through small groin incisions have been adopted. A successful 2005 congressional campaign to fund screening for aortic aneurysms brought the disease to national attention and symbolizes current confidence in curing it. Drawing on various published and unpublished sources, this paper elucidates the development of specific treatments for aortic aneurysms over time and more broadly addresses how medicine and surgery apply the knowledge and technology available in particular eras to treat a specific, identifiable, and lethal disease. Examining the evolution of these therapeutic efforts unveils broader trends in the history of medicine. This allows aortic aneurysms to serve as a case study for exploring shifting philosophies in medical history.

Pathogenesis of solitary right aortic arch: a mass effect hypothesis based on observations of serial human embryonic sections.

PubMed

Jin, Zhe W; Yamada, Tomonori; Kim, Ji H; Rodríguez-Vázquez, José F; Murakami, Gen; Arakawa, Keiji

2017-03-01

In general, solitary right aortic arch carries the left-sided ductus arteriosus communicating between the left subclavian and pulmonary arteries or the right-sided ductus connecting the descending aorta to the left pulmonary artery. Serial sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses suggested that the pathogenesis was unrelated to inversion due to dysfunction in gene cascades that control the systemic left/right axis. With inversion, conversely, the ductus or the sixth pharyngeal arch artery should connect to the right pulmonary artery. The disappearance of the right aortic arch started before the caudal migration of the aortic attachment of the ductus. Sympathetic nerve ganglia developed immediately posterior to both aortae, with a single embryonic specimen showing a large ganglion at the midline close to the union of the aortic arches. These ganglia may interfere with blood flow through the distal left arch, resulting in the ductus ending at the descending aorta behind the oesophagus. In another fetus examined, a midline shift of the ductus course resulted in the trachea curving posteriorly. Therefore, solitary right arch is likely to accompany abnormalities of the surrounding structures. The timing and site of the obstruction should be different between types: an almost midline obstruction near the aortic union needed for the development of the left-sided ductus and a distal obstruction near the left subclavian arterial origin needed for the development of the right-sided ductus. A mass effect of the sympathetic ganglia may explain the pathogenesis of any type of anomalous ductus arteriosus shown in previous reports of the solitary right arch.

Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices.

PubMed

Venkataraman, Lavanya; Sivaraman, Balakrishnan; Vaidya, Pratik; Ramamurthi, Anand

2016-12-01

The degradation of elastic matrix in the infrarenal aortic wall is a critical parameter underlying the formation and progression of abdominal aortic aneurysms. It is mediated by the chronic overexpression of matrix metalloprotease (MMP)-2 and MMP-9, leading to a progressive loss of elasticity and weakening of the aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently coaxing cell-based regenerative repair of the elastic matrix represents a potential strategy for slowing or arresting abdominal aortic aneurysm growth. Previous studies have demonstrated elastogenic induction of healthy and aneurysmal aortic smooth muscle cells and inhibition of MMPs, following exogenous delivery of elastogenic factors such as transforming growth factor (TGF)-β1, as well as MMP-inhibitors such as doxycycline (DOX) in two-dimensional culture. Based on these findings, and others that demonstrated elastogenic benefits of nanoparticulate delivery of these agents in two-dimensional culture, poly(lactide-co-glycolide) nanoparticles were developed for localized, controlled and sustained delivery of DOX and TGF-β1 to human aortic smooth muscle cells within a three-dimensional gels of type I collagen, which closely simulate the arterial tissue microenvironment. DOX and TGF-β1 released from these nanoparticles influenced elastogenic outcomes positively within the collagen constructs over 21 days of culture, which were comparable to that induced by exogenous supplementation of DOX and TGF-β1 within the culture medium. However, this was accomplished at doses ~20-fold lower than the exogenous dosages of the agents, illustrating that their localized, controlled and sustained delivery from nanoparticles embedded within a three-dimensional scaffold is an efficient strategy for directed elastogenesis. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Male gender and smoking are related to single, but not to multiple, human aortic aneurysms.

PubMed

Gutierrez, Paulo S; Leite, Thiago N P; Mangione, Fernanda M

2015-01-01

There is scanty information concerning multiple aortic aneurysms. Thus, we verified if clinical or pathological characteristics are different in patients with multiple (two or more) aortic aneurysms in comparison with those with only one. We selected at the necropsy files of the Heart Institute, São Paulo University School of Medicine, the last 100 cases with aortic aneurysms, comparing between the two groups: sex, age, presence of systemic arterial hypertension, diabetes, dyslipedemia, history of smoking habit, cause of the aneurysm, cause of death, and if the diagnosis was reached during life. Age was analysed by Mann-Whitney test, and the other variables by chi-square or Fisher's exact test. Multiple aneurysms corresponded to 14% of cases. The proportion of women among patients with multiple aneurysms was higher than among those with single aneurysm (64.3% versus 20.9%, P<.01), even if only cases with atherosclerosis were taken into consideration (women among multiple-6/10, 60.0%; among single-14/70, 20.0%; P=.01). Smoking was less reported in cases with multiple (4/14, 28.6%) than with single aneurysm (53/86, 61.6%; P=.04); considering cases with atherosclerosis, such difference decreases (40.0% of multiple versus 68.6% of single, P=.09). although atherosclerosis is present in most cases of both single and multiple aortic aneurysms, male gender and smoking, considered highly influential in such lesions, are less frequent in patients with multiple than in patients with single aneurysms. Thus mechanisms underlying multiple aortic aneurysms are probably different from those related to single, more common aneurysms. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the safety and efficacy of transcatheter aortic valve implantation in patients with a severe stenotic bicuspid aortic valve in a Chinese population*

PubMed Central

Liu, Xian-bao; Jiang, Ju-bo; Zhou, Qi-jing; Pu, Zhao-xia; He, Wei; Dong, Ai-qiang; Feng, Yan; Jiang, Jun; Sun, Yong; Xiang, Mei-xiang; He, Yu-xin; Fan, You-qi; Dong, Liang; Wang, Jian-an

2015-01-01

Objective: The purpose of this study is to evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with a severe stenotic bicuspid aortic valve (BAV) in a Chinese population. While several groups have reported the feasibility, efficacy, and safety of TAVI for patients with a BAV, worldwide experience of the technique is still limited, especially in China. Methods: From March 2013 to November 2014, high surgical risk or inoperable patients with symptomatic severe aortic stenosis (AS) who had undergone TAVI at our institution were selected for inclusion in our study. Results were compared between a BAV group and a tricuspid aortic valve (TAV) group. Results: Forty patients were included in this study, 15 (37.5%) of whom were identified as having a BAV. In the BAV group, the aortic valve area was smaller ((0.47±0.13) vs. (0.59±0.14) cm2), the ascending aortic diameter was larger ((40.4±4.4) vs. (36.4±4.3) mm), and the concomitant aortic regurgitation was lower. No significant differences were found between the groups in the other baseline characteristics. No differences were observed either in the choice of access or valve size. The procedural success achieved in this study was 100%. There were no differences between groups in device success (86.7% vs. 88.0%), 30-d mortality (6.7% vs. 8.0%), or 30-d combined end point (13.3% vs. 12.0%). The incidences of new pacemaker implantation, paravalvular regurgitation and other complications, recovery of left ventricle ejection fraction and heart function were similar in both groups. Conclusions: Patients with a severely stenotic BAV can be treated with TAVI, and their condition after treatment should be similar to that of people with a TAV. PMID:25743122

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis

PubMed Central

Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana

2017-01-01

Objective Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). Methods AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. Results More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: NCT00092677 PMID:28698175

[Endovascular repair of primary retrograde Stanford type A aortic dissection].

PubMed

Wu, H W; Sun, L; Li, D M; Jing, H; Xu, B; Wang, C T; Zhang, L

2016-10-01

Objective: To summarize the short- and mid-term results on endovascular repair of primary retrograde Stanford type A aortic dissection with an entry tear in distal aortic arch or descending aorta. Methods: Between December 2009 and December 2014, 21 male patients of primary retrograde Stanford type A aortic dissection with a mean age of (52±9) years received endovascular repair in Department of Cardiothoracic Surgery, Jinling Hospital. Among the 21 cases, 17 patients were presented as ascending aortic intramural hematoma, 4 patients as active blood flow in false lumen and partial thrombosis, 8 patients as ulcer on descending aorta combined intramural hematoma in descending aorta, and 13 patients as typical dissection changes. All patients received endovascular stent-graft repair successfully, with 15 cases in acute phase and 6 cases in chronic phase. Results: Cone stent was implanted in 13 cases, while straight stent in 8 cases, including 1 case of left common carotid-left subclavian artery bypass surgery and 1 case of restrictive bare-metal stent implantation. No perioperative stroke, paraplegia, stent fracture or displacement, limbs or abdominal organ ischemia or other severe complications occured, except for tracheotomy in 2 patients. Active blood flow in ascending aorta or aortic arch disappeared, and intramural hematoma started being absorbed on CT angiography images before discharge. All patients were alive during follow-up (6 to 72 months), and intramural hematoma in ascending aorta and aortic arch was absorbed thoroughly. Type Ⅰ endoleak and ulcer expansion were found in 1 patient, and type Ⅳ endoleak in distal stent was found in another one patient. Secondary ascending aortic dissection was found in 1 case two years later, which was cured by hybrid procedure with cardiopulmonary bypass. Conclusion: Endovascular repair of primary retrograde Stanford type A aortic dissection was safe and effective, which correlated with favorable short- and mid-term results.

Changes in Aortic Pulse Wave Velocity and the Predictors of Improvement in Arterial Stiffness Following Aortic Valve Replacement

PubMed Central

Cantürk, Emir; Çakal, Beytullah; Karaca, Oğuz; Omaygenç, Onur; Salihi, Salih; Akçevin, Atıf

2017-01-01

Background: The interaction between valvular aortic stenosis (AS) and arterial stiffness, as well as the impact of aortic valve replacement (AVR) on arterial stiffness, remains unclear. In this study, we aimed to evaluate the degree of AS severity on non-invasive pulse wave velocity (PWV) measurements. We also searched whether the AVR procedure favorably affects PWV. Methods: In all, 38 patients undergoing AVR for chronic AS were included. The degree of aortic stiffness was measured with PWV at both baseline and 6 months after AVR. Improvement in aortic stiffness was defined as the absolute decrease in PWV at 6 months compared to the baseline value. Results: The study population had a mean age of 59 ± 16 years, mean aortic gradient of 47.1 ± 6.4 mmHg, and mean aortic valve area (AVA) index of 0.45 ± 0.11 cm2/m2. Baseline PWV values correlated positively with the mean aortic gradient (r = 0.350, p = 0.031) and negatively with the AVA index (r = −0.512, p = 0.001). The mean PWV improved in 20 patients (53%) and worsened in 18 patients (47%). The baseline New York Heart Association (NYHA) class (odds ratio [OR] = 1.023, 95% confidence interval [CI] = 1.005–1.041, p = 0.041) and AVA index (OR = 1.040, 96% CI = 1.023–1.057, p = 0.028) emerged as the independent predictors of improvement in PWV following AVR. Conclusion: The severity of AS was significantly associated with baseline PWV. In general, the mean PWV did not change with AVR. Baseline NYHA class and the AVA index independently predicted PWV improvement following AVR. Since the change in PWV after AVR was polarized based on the patients’ characteristics, such as preoperative NYHA functional class or AVA index, further studies are needed to confirm clinical significance of PWV change following AVR in severe AS patients. PMID:28890466

Optimal prosthesis sizing in transcatheter aortic valve implantation by exclusive use of three-dimensional transoesophageal echocardiography.

PubMed

Kretzschmar, Daniel; Lauten, Alexander; Goebel, Bjoern; Doenst, Torsten; Poerner, Tudor C; Ferrari, Markus; Figulla, Hans R; Hamadanchi, Ali

2016-03-01

The assessment of aortic annular size is critical, and inappropriate sizing is thought to be a main reason of paravalvular aortic regurgitation. Multidetector computed tomograph is associated with the risk of contrast nephropathy. For optimal evaluation of the complex structure of the aortic annulus, three-dimensional (3D)-methods should be used. We therefore sought to determine the value of 3D-transoesophageal echocardiography (3D-TEE) for appropriate sizing. Hundred and one patients (mean age 81·4 years) with symptomatic aortic valve stenosis (AS) and high surgical risk profile (mean log. EuroScore 28·8%) being scheduled for transcatheter aortic valve implantation (TAVI) were included. 2D- and 3D-TEE were performed before the procedure to evaluate the aortic annulus diameter. Maximum, minimum and mean (max diameter + min diameter/2) annulus diameters were 24·7, 23·1 and 23. 9 mm in 3D-TEE and compared to 22·6 mm in 2D-TEE (P<0·001; 0·07; <0·001). The interobserver variability for 3D-TEE was low with a mean difference of 0·18 mm compared to 2D-TEE with 0·59 mm. The application of 3D-TEE caused a change of prosthesis size selection in 40% of patients compared to 2D-TEE. In this study, we implanted three different types of catheter-mounted valves (Edwards-SAPIEN(™) XT valve, CoreValve(™) and JenaValve(™) ). Final angiography confirmed valve competence (mild insufficiency) in 91%, and there was no aortic regurgitation greater than moderate in the follow-up echocardiographic evaluation. Assessment of aortic annulus dimensions for TAVI size selection can safely be performed with 3D-TEE only. Based on our results with significantly higher annulus diameter compared to 2D-TEE, we recommend 3D-TEE to reduce prosthesis undersizing. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Development of a consensus protocol to quantify primate anti-non-Gal xenoreactive antibodies using pig aortic endothelial cells.

PubMed

Azimzadeh, Agnes M; Byrne, Guerard W; Ezzelarab, Mohamed; Welty, Emily; Braileanu, Gheorghe; Cheng, Xiangfei; Robson, Simon C; McGregor, Christopher G A; Cooper, David K C; Pierson, Richard N

2014-01-01

Scientists working in the field of xenotransplantation do not employ a uniform method to measure and report natural and induced antibody responses to non-Galα(1,3)Gal (non-Gal) epitopes. Such humoral responses are thought to be particularly pathogenic after transplantation of vascularized GalTKO pig organs and having a more uniform assay and reporting format would greatly facilitate comparisons between laboratories. Flow cytometry allows examination of antibody reactivity to intact antigens in their natural location and conformation on cell membranes. We have established a simple and reproducible flow cytometric assay to detect antibodies specific for non-Gal pig antigens using primary porcine aortic endothelial cells (pAECs) and cell culture-adapted pAEC cell lines generated from wild type and α1,3galactosyl transferase knockout (GalTKO) swine. The consensus protocol we propose here is based on procedures routinely used in four xenotransplantation centers and was independently evaluated at three sites using shared cells and serum samples. Our observation support use of the cell culture-adapted GalTKO pAEC KO:15502 cells as a routine method to determine the reactivity of anti-non-Gal antibodies in human and baboon serum. We have developed an assay that allows the detection of natural and induced non-Gal xenoreactive antibodies present in human or baboon serum in a reliable and consistent manner. This consensus assay and format for reporting the data should be accessible to laboratories and will be useful for assessing experimental results between multiple research centers. Adopting this assay and format for reporting the data should facilitate the detection, monitoring, and detailed characterization of non-Gal antibody responses. © 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

The anatomy and development of normal and abnormal coronary arteries.

PubMed

Spicer, Diane E; Henderson, Deborah J; Chaudhry, Bill; Mohun, Timothy J; Anderson, Robert H

2015-12-01

At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death.

Incremental balloon deflation following complete resuscitative endovascular balloon occlusion of the aorta results in steep inflection of flow and rapid reperfusion in a large animal model of hemorrhagic shock.

PubMed

Davidson, Anders J; Russo, Rachel M; Ferencz, Sarah-Ashley E; Cannon, Jeremy W; Rasmussen, Todd E; Neff, Lucas P; Johnson, M Austin; Williams, Timothy K

2017-07-01

To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines. Eight Yorkshire-cross swine were splenectomized, instrumented, and subjected to rapid 25% total blood volume hemorrhage. After 30 minutes of shock, animals received 60 minutes of Zone 1 REBOA with a low-profile REBOA catheter. During subsequent resuscitation with shed blood, the aortic occlusion balloon was gradually deflated in stepwise fashion at the rate of 0.5 mL every 30 seconds until completely deflated. Aortic flow rate and proximal mean arterial pressure (MAP) were measured continuously over the period of balloon deflation. Graded balloon deflation resulted in variable initial return of aortic flow (median, 78 seconds; interquartile range [IQR], 68-105 seconds). A rapid increase in aortic flow during a single-balloon deflation step was observed in all animals (median, 819 mL/min; IQR, 664-1241 mL/min) and corresponded with an immediate decrease in proximal MAP (median, 30 mm Hg; IQR, 14.5-37 mm Hg). Total balloon volume and time to return of flow demonstrated no correlation (r = 0.016). This study is the first to characterize aortic flow during balloon deflation following REBOA. A steep inflection point occurs during balloon deflation that results in an abrupt increase in aortic flow and a concomitant decrease in MAP. Furthermore, the onset of distal aortic flow was inconsistent across study animals and did not correlate with initial balloon volume or relative deflation volume. Future studies to define the factors that affect aortic flow during balloon deflation are needed to facilitate controlled reperfusion following REBOA.

Hemiarch versus total aortic arch replacement in acute type A dissection: a systematic review and meta-analysis

PubMed Central

Poon, Shi Sum; Theologou, Thomas; Harrington, Deborah; Kuduvalli, Manoj; Oo, Aung

2016-01-01

Background Despite recent advances in aortic surgery, acute type A aortic dissection remains a surgical emergency associated with high mortality and morbidity. Appropriate management is crucial to achieve satisfactory outcomes but the optimal surgical approach is controversial. The present systematic review and meta-analysis sought to access cumulative data from comparative studies between hemiarch and total aortic arch replacement in patients with acute type A aortic dissection. Methods A systematic review of the literature using six databases. Eligible studies include comparative studies on hemiarch versus total arch replacement reporting short, medium and long term outcomes. A meta-analysis was performed on eligible studies reporting outcome of interest to quantify the effects of hemiarch replacement on mortality and morbidity risk compared to total arch replacement. Result Fourteen retrospective studies met the inclusion criteria and 2,221 patients were included in the final analysis. Pooled analysis showed that hemiarch replacement was associated with a lower risk of post-operative renal dialysis [risk ratio (RR) =0.72; 95% confidence interval (CI): 0.56–0.94; P=0.02; I2=0%]. There was no significant difference in terms of in-hospital mortality between the two groups (RR =0.84; 95% CI: 0.65–1.09; P=0.20; I2=0%). Cardiopulmonary bypass, aortic cross clamp and circulatory arrest times were significantly longer in total arch replacement. During follow up, no significant difference was reported from current studies between the two operative approaches in terms of aortic re-intervention and freedom from aortic reoperation. Conclusions Within the context of publication bias by high volume aortic centres and non-randomized data sets, there was no difference in mortality outcomes between the two groups. This analysis serves to demonstrate that for those centers doing sufficient total aortic arch activity to allow for publication, excellent and equivalent outcomes are achievable. Conclusions on differences in longer term outcome data are required. We do not, however, advocate total arch as a primary approach by all centers and surgeons irrespective of patient characteristics, but rather, a tailored approach based on surgeon and center experience and patient presentation. PMID:27386403

Results of open pararenal abdominal aortic aneurysm repair: single centre series and pooled analysis of literature.

PubMed

van Lammeren, Guus W; Ünlü, Çağdaş; Verschoor, Sjoerd; van Dongen, Eric P; Wille, Jan; van de Pavoordt, Eric Dwm; de Vries-Werson, Debbie Ab; De Vries, Jean-Paul Pm

2017-06-01

Objectives Endovascular treatment of pararenal abdominal aortic aneurysm has gained terrain over the past decade, despite the substantial need for reinterventions during follow-up. However, open repair is still a well-established treatment option. With the current study we report the results of a consecutive series of elective primary open pararenal abdominal aortic aneurysm repair in a tertiary vascular referral centre, combined with an overview of current literature and pooled data analysis of perioperative mortality of open and endovascular pararenal abdominal aortic aneurysm repair. Methods A retrospective analysis of a prospective database of all elective open pararenal abdominal aortic aneurysm repairs in the St. Antonius Hospital between 2005 and 2014 was performed. Primary endpoint was 30-day mortality. Secondary endpoints were 30-day morbidity, new onset dialysis, reintervention free survival, and overall survival during follow-up. Results Between 2005 and 2014, 214 consecutive patients underwent elective open pararenal abdominal aortic aneurysm repair. Mean age was 69.8 (±7.1) years, 82.7% (177/214) were men, and mean abdominal aortic aneurysm diameter was 62 (±11) mm. Thirty-day mortality was 3.4%. Thirty-day morbidity was 27.1%, which predominantly consisted of pneumonia (18.7% (40/214)), cardiac events (3.3% (7/214)), and new onset dialysis (2.8% (6/214)). Estimated five-year overall survival rate was 74.2%. 0.9% (2/214) of patients required abdominal aortic aneurysm-related reintervention, and an additional 2.3% (5/214) required surgical repair of an incisional hernia. Pooled analysis of literature revealed a 30-day mortality of 3.0% for open pararenal repair and 1.9% for fenestrated endovascular repair. Conclusion Open pararenal abdominal aortic aneurysm repair in the era of increasing endovascular options results in acceptable perioperative morbidity and mortality rates. Mid-term reintervention rate is low compared to fenestrated endovascular aneurysm repair. Expertise with open repair still remains essential for treatment of pararenal abdominal aortic aneurysms in the near future, especially for those patients that are declined for endovascular treatment.

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB*

PubMed Central

Inoue, Tomoaki; Kobayashi, Kunihisa; Inoguchi, Toyoshi; Sonoda, Noriyuki; Fujii, Masakazu; Maeda, Yasutaka; Fujimura, Yoshinori; Miura, Daisuke; Hirano, Ken-ichi; Takayanagi, Ryoichi

2011-01-01

We examined the effects of adipose triglyceride lipase (ATGL) on the initiation of atherosclerosis. ATGL was recently identified as a rate-limiting triglyceride (TG) lipase. Mutations in the human ATGL gene are associated with neutral lipid storage disease with myopathy, a rare genetic disease characterized by excessive accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, shows massive TG accumulation in both coronary atherosclerotic lesions and the myocardium. Recent reports show that myocardial triglyceride content is significantly higher in patients with prediabetes or diabetes and that ATGL expression is decreased in the obese insulin-resistant state. Therefore, we investigated the effect of decreased ATGL activity on the development of atherosclerosis using human aortic endothelial cells. We found that ATGL knockdown enhanced monocyte adhesion via increased expression of TNFα-induced intercellular adhesion molecule-1 (ICAM-1). Next, we determined the pathways (MAPK, PKC, or NFκB) involved in ICAM-1 up-regulation induced by ATGL knockdown. Both phosphorylation of PKC and degradation of IκBα were increased in ATGL knockdown human aortic endothelial cells. In addition, intracellular diacylglycerol levels and free fatty acid uptake via CD36 were significantly increased in these cells. Inhibition of the PKC pathway using calphostin C and GF109203X suppressed TNFα-induced ICAM-1 expression. In conclusion, we showed that ATGL knockdown increased monocyte adhesion to the endothelium through enhanced TNFα-induced ICAM-1 expression via activation of NFκB and PKC. These results suggest that reduced ATGL expression may influence the atherogenic process in neutral lipid storage diseases and in the insulin-resistant state. PMID:21828047

Quantification and comparison of the mechanical properties of four human cardiac valves.

PubMed

Pham, Thuy; Sulejmani, Fatiesa; Shin, Erica; Wang, Di; Sun, Wei

2017-05-01

Although having the same ability to permit unidirectional flow within the heart, the four main valves-the mitral valve (MV), aortic (AV), tricuspid (TV) and pulmonary (PV) valves-experience different loading conditions; thus, they exhibit different structural integrity from one another. Most research on heart valve mechanics have been conducted mainly on MV and AV or an individual valve, but none quantify and compare the mechanical and structural properties among the four valves from the same aged patient population whose death was unrelated to cardiovascular disease. A total of 114 valve leaflet samples were excised from 12 human cadavers whose death was unrelated to cardiovascular disease (70.1±3.7years old). Tissue mechanical and structural properties were characterized by planar biaxial mechanical testing and histological methods. The experimental data were then fitted with a Fung-type constitutive model. The four valves differed substantially in thickness, degree of anisotropy, and stiffness. The leaflets of the left heart (the AV leaflets and the anterior mitral leaflets, AML) were significantly stiffer and less compliant than their counterparts in the right heart. TV leaflets were the most extensible and isotropic, while AML and AV leaflets were the least extensible and the most anisotropic. Age plays a significant role in the reduction of leaflet stiffness and extensibility with nearly straightened collagen fibers observed in the leaflet samples from elderly groups (65years and older). Results from 114 human leaflet samples not only provided a baseline quantification of the mechanical properties of aged human cardiac valves, but also offered a better understanding of the age-dependent differences among the four valves. It is hoped that the experimental data collected and the associated constitutive models in this study can facilitate future studies of valve diseases, treatments and the development of interventional devices. Most research on heart valve mechanics have been conducted mainly on mitral and aortic valves or an individual valve, but none quantify and compare the mechanical and structural properties among the four valves from the same relatively healthy elderly patient population. In this study, the mechanical and microstructural properties of 114 leaflets of aortic, mitral, pulmonary and tricuspid valves from 12 human cadaver hearts were mechanically tested, analyzed and compared. Our results not only provided a baseline quantification of the mechanical properties of aged human valves, but a age range between patients (51-87years) also offers a better understanding of the age-dependent differences among the four valves. It is hoped that the obtained experimental data and associated constitutive parameters can facilitate studies of valve diseases, treatments and the development of interventional devices. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces.

PubMed

Ajay, M; Chai, H J; Mustafa, A M; Gilani, A H; Mustafa, M R

2007-02-12

Previous studies have demonstrated the anti-hypertensive effects of Hibiscus sabdariffa L. (HS) in both humans and experimental animals. To explore the mechanisms of the anti-hypertensive effect of the HS, we examined the effects of a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration-dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre-contracted aortic rings, with a greater potency against the alpha(1)-adrenergic receptor agonist. The relaxant effect of HSE was partly dependent on the presence of a functional endothelium as the action was significantly reduced in endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM), significantly blocked the relaxant effects of HSE. Endothelium-dependent and -independent relaxations induced by acetylcholine and sodium nitroprusside, respectively, were significantly enhanced in aortic rings pretreated with HSE when compared to those observed in control aortic rings. The present results demonstrated that HSE has a vasodilator effect in the isolated aortic rings of hypertensive rats. These effects are probably mediated through the endothelium-derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))-influx into vascular smooth muscle cells. The present data further supports previous in vivo findings and the traditional use of HS as an anti-hypertensive agent.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

PubMed

Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L

2013-04-01

Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

Restoration of Circulating MFGE8 (Milk Fat Globule-EGF Factor 8) Attenuates Cardiac Hypertrophy Through Inhibition of Akt Pathway.

PubMed

Deng, Ke-Qiong; Li, Jing; She, Zhi-Gang; Gong, Jun; Cheng, Wen-Lin; Gong, Fu-Han; Zhu, Xue-Yong; Zhang, Yan; Wang, Zhihua; Li, Hongliang

2017-10-01

Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients. Deleting Mfge8 in mice maintained normal heart function at basal level but substantially exacerbated the hypertrophic enlargement of cardiomyocytes, reprogramming of pathological genes, contractile dysfunction, and myocardial fibrosis after aortic banding surgery. In contrast, cardiac-specific Mfge8 overexpression in transgenic mice significantly blunted aortic banding-induced cardiac hypertrophy. Whereas MAPK (mitogen-activated protein kinase) pathways were unaffected in either Mfge8 -knockout or Mfge8 -overexpressing mice, the activated Akt/PKB (protein kinase B)-Gsk-3β (glycogen synthase kinase-3β)/mTOR (mammalian target of rapamycin) pathway after aortic banding was significantly potentiated by Mfge8 deficiency but suppressed by Mfge8 overexpression. Inhibition of Akt with MK-2206 blocked the prohypertrophic effects of Mfge8 deficiency in angiotensin II-treated neonatal rat cardiomyocytes. Finally, administering a recombinant human MFGE8 in mice in vivo alleviated cardiac hypertrophy induced by aortic banding. Our findings indicate that Mfge8 is an endogenous negative regulator of pathological cardiac hypertrophy and may, thus, have potential both as a novel biomarker and as a therapeutic target for treatment of cardiac hypertrophy. © 2017 American Heart Association, Inc.

Use of human fibrinogen concentrate during proximal aortic reconstruction with deep hypothermic circulatory arrest.

PubMed

Hanna, Jennifer M; Keenan, Jeffrey E; Wang, Hanghang; Andersen, Nicholas D; Gaca, Jeffrey G; Lombard, Frederick W; Welsby, Ian J; Hughes, G Chad

2016-02-01

Human fibrinogen concentrate (HFC) is approved by the Food and Drug Administration for use at 70 mg/kg to treat congenital afibrinogenemia. We sought to determine whether this dose of HFC increases fibrinogen levels in the setting of high-risk bleeding associated with aortic reconstruction and deep hypothermic circulatory arrest (DHCA). This was a prospective, pilot, off-label study in which 22 patients undergoing elective proximal aortic reconstruction with DHCA were administered 70 mg/kg HFC upon separation from cardiopulmonary bypass (CPB). Fibrinogen levels were measured at baseline, just before, and 10 minutes after HFC administration, on skin closure, and the day after surgery. The primary study outcome was the difference in fibrinogen level immediately after separation from CPB, when HFC was administered, and the fibrinogen level 10 minutes following HFC administration. Additionally, postoperative thromboembolic events were assessed as a safety analysis. The mean baseline fibrinogen level was 317 ± 49 mg/dL and fell to 235 ± 39 mg/dL just before separation from CPB. After HFC administration, the fibrinogen level rose to 331 ± 41 mg/dL (P < .001) and averaged 372 ± 45 mg/dL the next day. No postoperative thromboembolic complications occurred. Administration of 70 mg/kg HFC upon separation from CPB raises fibrinogen levels by approximately 100 mg/dL without an apparent increase in thrombotic complications during proximal aortic reconstruction with DHCA. Further prospective study in a larger cohort of patients will be needed to definitively determine the safety and evaluate the efficacy of HFC as a hemostatic adjunct during these procedures. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Role of modern 3D echocardiography in valvular heart disease

PubMed Central

2014-01-01

Three-dimensional (3D) echocardiography has been conceived as one of the most promising methods for the diagnosis of valvular heart disease, and recently has become an integral clinical tool thanks to the development of high quality real-time transesophageal echocardiography (TEE). In particular, for mitral valve diseases, this new approach has proven to be the most unique, powerful, and convincing method for understanding the complicated anatomy of the mitral valve and its dynamism. The method has been useful for surgical management, including robotic mitral valve repair. Moreover, this method has become indispensable for nonsurgical mitral procedures such as edge to edge mitral repair and transcatheter closure of paravaluvular leaks. In addition, color Doppler 3D echo has been valuable to identify the location of the regurgitant orifice and the severity of the mitral regurgitation. For aortic and tricuspid valve diseases, this method may not be quite as valuable as for the mitral valve. However, the necessity of 3D echo is recognized for certain situations even for these valves, such as for evaluating the aortic annulus for transcatheter aortic valve implantation. It is now clear that this method, especially with the continued development of real-time 3D TEE technology, will enhance the diagnosis and management of patients with these valvular heart diseases. PMID:25378966

Physiological rules for the heart, lungs and other pressure-based organs

PubMed Central

Camilleri, Liberato; Manché, Alexander; Gatt, Ruben; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Grima, Joseph N.; Chetcuti, Stanley

2017-01-01

Background The adherence of the heart to physical laws, such as Laplace’s Law, may act as a measure of the organ’s relative efficiency. Allometric relationships were investigated to assess the heart’s efficiency concerning end-diastolic and end-systolic volumes, cardiac pressurization energy, cardiac output and mass. Methods Data to generate allometric relationships was obtained using a literature search, identifying heart and lung data across different mammalian and bird species. Statistical analysis was carried out using ordinary least squares (OLS) estimation. Results Near isometric relationships exist between body mass and seven parameters indicating no “efficiency of size” with scaling of the heart, and size-matching of the heart to the lungs and whole body. Even though there was equal efficiency in pressurization energy generation, cardiac output was maximally efficient in small mammals <10 kg and birds; the human heart reached only 71% efficiency. This loss in cardiac efficiency with increasing body mass can be explained by the aortic cross-section that scales following the three-quarter allometry law, compared to end-systolic and end-diastolic volumes that scale isometrically. The heart is therefore throttled by a relatively small aorta at large body size. Conclusions Mammalian and avian hearts operate at similar efficiencies, demonstrating a high degree of symmorphosis, however cardiac output efficiency decreases in larger animals due to a relatively negative aortic cross-section allometry. This work has a myriad of potential applications including explaining cardiac dysfunction in athletes, patient-prosthesis mismatch in aortic valve replacement and why heavy exercise is associated with a worse prognosis than mild or moderate exercise. PMID:29268387

Viscous Energy Loss in the Presence of Abnormal Aortic Flow

PubMed Central

Barker, A.J.; van Ooij, P.; Bandi, K.; Garcia, J.; Albaghdadi, M.; McCarthy, P.; Bonow, R. O.; Carr, J.; Collins, J.; Malaisrie, C.; Markl, M.

2014-01-01

Purpose To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses, and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Methods 4D flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n=12, age=37±10), patients with aortic dilation (n=16, age=52±8), and patients with aortic valve stenosis matched for age and aortic size (n=14, age=46±15), using a relationship between the 3D velocity field and viscous energy dissipation. Results Viscous energy loss was significantly elevated in the thoracic aorta for patients with dilated aorta (3.6±1.3 mW, p=0.024) and patients with aortic stenosis (14.3±8.2 mW, p<0.001) compared to healthy volunteers (2.3±0.9 mW). The same pattern of significant differences were seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2±1.1 mW, p=0.021) and patients with aortic stenosis (10.9±6.8 mW, p<0.001) were elevated compared to healthy volunteers (1.2±0.6 mW). Conclusion This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow. PMID:24122967

Influence of the tilt angle of Percutaneous Aortic Prosthesis on Velocity and Shear Stress Fields

PubMed Central

Gomes, Bruno Alvares de Azevedo; Camargo, Gabriel Cordeiro; dos Santos, Jorge Roberto Lopes; Azevedo, Luis Fernando Alzuguir; Nieckele, Ângela Ourivio; Siqueira-Filho, Aristarco Gonçalves; de Oliveira, Glaucia Maria Moraes

2017-01-01

Background Due to the nature of the percutaneous prosthesis deployment process, a variation in its final position is expected. Prosthetic valve placement will define the spatial location of its effective orifice in relation to the aortic annulus. The blood flow pattern in the ascending aorta is related to the aortic remodeling process, and depends on the spatial location of the effective orifice. The hemodynamic effect of small variations in the angle of inclination of the effective orifice has not been studied in detail. Objective To implement an in vitro simulation to characterize the hydrodynamic blood flow pattern associated with small variations in the effective orifice inclination. Methods A three-dimensional aortic phantom was constructed, reproducing the anatomy of one patient submitted to percutaneous aortic valve implantation. Flow analysis was performed by use of the Particle Image Velocimetry technique. The flow pattern in the ascending aorta was characterized for six flow rate levels. In addition, six angles of inclination of the effective orifice were assessed. Results The effective orifice at the -4º and -2º angles directed the main flow towards the anterior wall of the aortic model, inducing asymmetric and high shear stress in that region. However, the effective orifice at the +3º and +5º angles mimics the physiological pattern, centralizing the main flow and promoting a symmetric distribution of shear stress. Conclusion The measurements performed suggest that small changes in the angle of inclination of the percutaneous prosthesis aid in the generation of a physiological hemodynamic pattern, and can contribute to reduce aortic remodeling. PMID:28793046

Acute effects of ultrafiltration on aortic mechanical properties determined by measurement of pulse wave velocity and pulse propagation time in hemodialysis patients

PubMed Central

Yıldız, Banu Şahin; Şahin, Alparslan; Aladağ, Nazire Başkurt; Arslan, Gülgün; Kaptanoğulları, Hakan; Akın, İbrahim; Yıldız, Mustafa

2015-01-01

Objective: The effects of acute hemodialysis session on pulse wave velocity are conflicting. The aim of the current study was to assess the acute effects of ultrafiltration on the aortic mechanical properties using carotid-femoral (aortic) pulse wave velocity and pulse propagation time. Methods: A total of 26 (12 women, 14 men) consecutive patients on maintenance hemodialysis (mean dialysis duration: 40.7±25.6 (4-70) months) and 29 healthy subjects (13 women, 16 men) were included in this study. Baseline blood pressure, carotid-femoral (aortic) pulse wave velocity, and pulse propagation time were measured using a Complior Colson device (Createch Industrie, France) before and immediately after the end of the dialysis session. Results: While systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse wave velocity were significantly higher in patients on hemodialysis than in healthy subjects, pulse propagation time was significantly higher in healthy subjects. Although body weight, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse wave velocity were significantly decreased, heart rate and pulse propagation time were significantly increased after ultrafiltration. There was a significant positive correlation between pulse wave velocity and age, body height, waist circumference, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and heart rate. Conclusion: Although hemodialysis treatment may chronically worsen aortic mechanical properties, ultrafiltration during hemodialysis may significantly improve aortic pulse wave velocity, which is inversely related to aortic distensibility and pulse propagation time. PMID:25413228

Computational assessment of model-based wave separation using a database of virtual subjects.

PubMed

Hametner, Bernhard; Schneider, Magdalena; Parragh, Stephanie; Wassertheurer, Siegfried

2017-11-07

The quantification of arterial wave reflection is an important area of interest in arterial pulse wave analysis. It can be achieved by wave separation analysis (WSA) if both the aortic pressure waveform and the aortic flow waveform are known. For better applicability, several mathematical models have been established to estimate aortic flow solely based on pressure waveforms. The aim of this study is to investigate and verify the model-based wave separation of the ARCSolver method on virtual pulse wave measurements. The study is based on an open access virtual database generated via simulations. Seven cardiac and arterial parameters were varied within physiological healthy ranges, leading to a total of 3325 virtual healthy subjects. For assessing the model-based ARCSolver method computationally, this method was used to perform WSA based on the aortic root pressure waveforms of the virtual patients. Asa reference, the values of WSA using both the pressure and flow waveforms provided by the virtual database were taken. The investigated parameters showed a good overall agreement between the model-based method and the reference. Mean differences and standard deviations were -0.05±0.02AU for characteristic impedance, -3.93±1.79mmHg for forward pressure amplitude, 1.37±1.56mmHg for backward pressure amplitude and 12.42±4.88% for reflection magnitude. The results indicate that the mathematical blood flow model of the ARCSolver method is a feasible surrogate for a measured flow waveform and provides a reasonable way to assess arterial wave reflection non-invasively in healthy subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early Identification of Aortic Valve Sclerosis Using Iron Oxide Enhanced MRI

PubMed Central

Hamilton, Amanda M.; Rogers, Kem A.; Belisle, Andre J.L.; Ronald, John A.; Rutt, Brian K.; Weissleder, Ralph; Boughner, Derek R.

2017-01-01

Purpose To test the ability of MION-47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS). Materials and Methods The aortic valves of control and cholesterol-fed New Zealand White rabbits were imaged in vivo pre- and 48 h post-intravenous administration of MION-47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION-47 aortic valve cusps were imaged ex vivo on a 3.0T whole-body MR system with a custom gradient insert coil and a three-dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol-fed contrast-free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake. Results MION-47 enhanced the visibility of both control and cholesterol-fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast-administered aortic valves. Signal voids were not observed in contrast-free valve cusps. In MION-47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol-fed valves but also in myofibroblasts from control and cholesterol-fed valves. Conclusion Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage-specific iron compound rather than passive targeting may be required. PMID:20027578

Prediction of aortic valvular area and gradient by noninvasive techniques.

PubMed

Cousins, A L; Eddleman, E E; Reeves, T J

1978-03-01

Sixty-two patients with isolated aortic valvular stenosis were analyzed by a series of common noninvasive procedures and by cardiac catheterization. The data from 50 of these were evaluated in a retrospective fashion by multiple regression methods to determine significant objectively obtained predictors of aortic-left ventricular gradient and valvular area. Formulae were derived from these analyses and an additional 12 patients were then studied prospectively to evaluate the validity of the predictive formulae. Forty-three of 50 patients (86 per cent) were correctly identified as to a gradient of greater or less than 50 mm. Hg in the initial group, and all those in the prospectively studied sample were correctly classified. Thiry-five of 43 patients (82 per cent) of those with valve area data in the first application were correctly classified as to valve area or greater or less than 0.8 cm.2, and all patients in the prospectively studied group were appropriately identified as to the same area. The combined application of the observations of calcification of the aortic valve, shudder waves on the anacrotic limb, prolonged time to peak of the percussion wave and alteration of the dicrotic notch of the carotid pulse tracing, left ventricular hypertrophy by electrocardiogram, and the altered duration of ventricular ejection time were reliable predictors of elevated aortic-left ventricular gradient and decreased aortic valvular size.

[Right-side aortic arch with aberrant left subclavian artery and Kommerell's diverticulum. A cause of vascular ring].

PubMed

Tamayo-Espinosa, Tania; Erdmenger-Orellana, Julio; Becerra-Becerra, Rosario; Balderrabano-Saucedo, Norma; Segura-Standford, Begoña

The right-side aortic arch may be associated with aberrant left subclavian artery, in some cases this artery originates from an aneurismal dilation of the aorta called Kommerell's diverticulum. A report is presented on 2 cases of vascular ring formed by a right-side aortic arch, anomalous left subclavian artery, Kommerell's diverticulum and left patent ductus arteriosus. A review the literature was also performed as regards the embryological development and the imaging methods used to help in the diagnosis of this rare vascular anomaly. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Optical coherence tomography assessment of vessel wall degradation in aneurysmatic thoracic aortas

NASA Astrophysics Data System (ADS)

Real, Eusebio; Eguizabal, Alma; Pontón, Alejandro; Val-Bernal, J. Fernando; Mayorga, Marta; Revuelta, José M.; López-Higuera, José; Conde, Olga M.

2013-06-01

Optical coherence tomographic images of ascending thoracic human aortas from aneurysms exhibit disorders on the smooth muscle cell structure of the media layer of the aortic vessel as well as elastin degradation. Ex-vivo measurements of human samples provide results that correlate with pathologist diagnosis in aneurysmatic and control aortas. The observed disorders are studied as possible hallmarks for aneurysm diagnosis. To this end, the backscattering profile along the vessel thickness has been evaluated by fitting its decay against two different models, a third order polynomial fitting and an exponential fitting. The discontinuities present on the vessel wall on aneurysmatic aortas are slightly better identified with the exponential approach. Aneurysmatic aortic walls present uneven reflectivity decay when compared with healthy vessels. The fitting error has revealed as the most favorable indicator for aneurysm diagnosis as it provides a measure of how uniform is the decay along the vessel thickness.

Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications.

PubMed

Moos, Philip J; Honeggar, Matthew; Malugin, Alexander; Herd, Heather; Thiagarajan, Giridhar; Ghandehari, Hamidreza

2013-08-05

Understanding the potential toxicities of manufactured nanoconstructs used for drug delivery and biomedical applications may help improve their safety. We sought to determine if surface-modified silica nanoparticles and poly(amido amine) dendrimers elicit genotoxic responses on vascular endothelial cells. The nanoconstructs utilized in this study had a distinct geometry (spheres vs worms) and surface charge, which were used to evaluate the contributions of these parameters to any potential adverse effects of these materials. Time-dependent cytotoxicity was found for surfaced-functionalized but geometrically distinct silica materials, while amine-terminated dendrimers displayed time-independent cytotoxicity and carboxylated dendrimers were nontoxic in our assays. Transcriptomic evaluation of human aortic endothelial cell (HAEC) responses indicated time-dependent gene induction following silica exposure, consisting of cell cycle gene repression and pro-inflammatory gene induction. However, the dendrimers did not induce genomic toxicity, despite displaying general cytotoxicity.

Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells

PubMed Central

Xi, Hang; Zhang, Yuling; Xu, Yanjie; Yang, William Y; Jiang, Xiaohua; Sha, Xiaojin; Cheng, Xiaoshu; Wang, Jingfeng; Qin, Xuebin; Yu, Jun; Ji, Yong; Yang, Xiaofeng; Wang, Hong

2016-01-01

Rationale Endothelial injury is an initial mechanism mediating cardiovascular disease. Objective Here, we investigated the effect of hyperhomocysteinemia (HHcy) on programed cell death in endothelial cells (EC). Methods and Results We established a novel flow-cytometric gating method to define pyrotosis (Annexin V−/Propidium iodide+). In cultured human EC, we found that: 1). Hcy and Lipopolysaccharide (LPS) individually and synergistically induced inflammatory pyroptotic and non-inflammatory apoptotic cell death. 2). Hcy/LPS induced caspase-1 activation prior to caspase-8, -9, -3 activations. 3). Caspase-1/3 inhibitors rescued Hcy/LPS-induced pyroptosis/apoptosis, but caspase-8/9 inhibitors had differential rescue effect. 4). Hcy/LPS induced NLRP3 protein, caused NLRP3-containing inflammasome assembly, caspase-1 activation and IL-1β cleavage/activation. 5). Hcy/LPS elevated intracellular reactive oxidative species (ROS). 6). Intracellular oxidative gradient determined cell death destiny as intermediate intracellular ROS levels are associated with pyroptosis, whereas, high ROS corresponded to apoptosis. 7). Hcy/LPS induced mitochondrial membrane potential collapse and cytochrome-c release, and increased Bax/Bcl-2 ratio which were attenuated by antioxidants and caspase-1 inhibitor. 8). Antioxidants extracellular superoxide dismutase and catalase prevented Hcy/LPS-induced caspase-1 activation, mitochondrial dysfunction and pyroptosis/apoptosis. In cystathionine β-synthase deficient (Cbs−/−) mice, severe HHcy induced caspase-1 activation in isolated lung EC and caspase-1 expression in aortic endothelium, and elevated aortic caspase-1,9 protein/activity and Bax/Bcl-2 ratio in Cbs−/− aorta and HUVEC. Finally, Hcy-induced DNA fragmentation was reversed in caspase-1−/− EC. HHcy-induced aortic endothelial dysfunction was rescued in caspase-1−/− and NLRP3−/− mice. Conclusion HHcy preferentially induces EC pyroptosis via caspase-1-dependent inflammasome activation leading to endothelial dysfunction. We termed caspase-1 responsive pyroptosis and apoptosis as pyrop-apoptosis. PMID:27006445

Energy loss in the left ventricle obtained by vector flow mapping as a new quantitative measure of severity of aortic regurgitation: a combined experimental and clinical study.

PubMed

Stugaard, Marie; Koriyama, Hikaru; Katsuki, Keiko; Masuda, Kasumi; Asanuma, Toshihiko; Takeda, Yasuharu; Sakata, Yasushi; Itatani, Keiichi; Nakatani, Satoshi

2015-07-01

In aortic regurgitation (AR), energy loss (EL) produced by inefficient turbulent flow may be a burden to the heart predicting decompensation. We attempted to quantify EL in AR induced in an acute dog model and in patients with chronic AR using novel echocardiographic method vector flow mapping (VFM). In 11 anaesthetized open-chest dogs, AR was induced by distorting the aortic valve with a pigtail catheter, in totally 20 cases. Regurgitant fraction was determined using pulsed Doppler echocardiography, <30% considered mild to moderate (Group 1, n = 11) and ≥30% moderate to severe (Group 2, n = 9). The clinical study consisted of 22 patients with various degrees of AR; 11 mild to moderate (Group 1) and 11 moderate to severe (Group 2), and compared with 12 normals. VFM is based on continuity equation applied to colour Doppler and speckle tracking velocities, acquired from apical long-axis image. EL was calculated frame by frame, averaged from three beats. In the dog study, diastolic EL increased significantly with severity of AR (baseline vs. Group 1 vs. Group 2: 3.8 ± 1.6 vs. 13.0 ± 5.0 vs. 22.4 ± 14.0 [J/(m s)], ANOVA P = 0.0001). Similar to dogs, diastolic EL also increased in humans by the severity of AR (control vs. Group 1 vs. Group 2: 2.8 ± 1.5 vs. 14.3 ± 11.5 vs. 18.6 ± 2.3 [J/(m s)], ANOVA P = 0.001). VFM provides a promising method to quantify diastolic EL in AR. Diastolic EL increases in AR proportional to its severity. EL may be useful to determine the severity of disease from the aspect of cardiac load. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Vortex dynamics in Patient-Specific Stenotic Tricuspid and Bicuspid Aortic Valves pre- and post- Trans-catheter Aortic Valve Replacement

NASA Astrophysics Data System (ADS)

Hatoum, Hoda; Dasi, Lakshmi Prasad

2017-11-01

Understanding blood flow related adverse complications such as leaflet thrombosis post-transcatheter aortic valve implantation (TAVI) requires a deeper understanding of how patient-specific anatomic and hemodynamic factors, and relative valve positioning dictate sinus vortex flow and stasis regions. High resolution time-resolved particle image velocimetry measurements were conducted in compliant and transparent 3D printed patient-specific models of stenotic bicuspid and tricuspid aortic valve roots from patients who underwent TAVI. Using Lagrangian particle tracking analysis of sinus vortex flows and probability distributions of residence time and blood damage indices we show that (a) patient specific modeling provides a more realistic assessment of TAVI flows, (b) TAVI deployment alters sinus flow patterns by significantly decreasing sinus velocity and vorticity, and (c) relative valve positioning can control critical vortex structures that may explain preferential leaflet thrombosis corresponding to separated flow recirculation, secondary to valve jet vectoring relative to the aorta axis. This work provides new methods and understanding of the spatio-temporal aortic sinus vortex dynamics in post TAVI pathology. This study was supported by the Ohio State University DHLRI Trifit Challenge award.

Sex, Aging, and Preexisting Cerebral Ischemic Disease in Patients With Aortic Stenosis

PubMed Central

Wang, Ping; Acker, Michael A.; Bilello, Michel; Melhem, Elias R.; Stambrook, Elizabeth; Ratcliffe, Sarah J.; Floyd, Thomas F.

2011-01-01

Background Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease. We tested the hypotheses that increasing age, female sex, coronary artery disease, and the severity of AS are predictive of the severity of preexisting cerebral ischemic lesions. Methods A total of 95 subjects were included in this study. Subjects were imaged on 1.5 Tesla magnetic resonance imaging scanners to obtain multimodal image sets which were used for the automatic segmentation of cerebral lesion volume. The dependence of lesion volume upon age, sex, coronary artery disease, and the severity of AS were tested. Results The results demonstrate a strong correlation between aging, female sex, and white matter and ischemia-like lesion volume in patients with aortic stenosis. Conclusions Women and those of advanced age presenting for aortic valve replacement for AS may incur a particularly high risk for postoperative neurologic sequelae due to an exceptional preexisting burden of cerebral ischemic disease. PMID:20868818

The influence of computational assumptions on analysing abdominal aortic aneurysm haemodynamics.

PubMed

Ene, Florentina; Delassus, Patrick; Morris, Liam

2014-08-01

The variation in computational assumptions for analysing abdominal aortic aneurysm haemodynamics can influence the desired output results and computational cost. Such assumptions for abdominal aortic aneurysm modelling include static/transient pressures, steady/transient flows and rigid/compliant walls. Six computational methods and these various assumptions were simulated and compared within a realistic abdominal aortic aneurysm model with and without intraluminal thrombus. A full transient fluid-structure interaction was required to analyse the flow patterns within the compliant abdominal aortic aneurysms models. Rigid wall computational fluid dynamics overestimates the velocity magnitude by as much as 40%-65% and the wall shear stress by 30%-50%. These differences were attributed to the deforming walls which reduced the outlet volumetric flow rate for the transient fluid-structure interaction during the majority of the systolic phase. Static finite element analysis accurately approximates the deformations and von Mises stresses when compared with transient fluid-structure interaction. Simplifying the modelling complexity reduces the computational cost significantly. In conclusion, the deformation and von Mises stress can be approximately found by static finite element analysis, while for compliant models a full transient fluid-structure interaction analysis is required for acquiring the fluid flow phenomenon. © IMechE 2014.

The utility of live video capture to enhance debriefing following transcatheter aortic valve replacement.

PubMed

Seamans, David P; Louka, Boshra F; Fortuin, F David; Patel, Bhavesh M; Sweeney, John P; Lanza, Louis A; DeValeria, Patrick A; Ezrre, Kim M; Ramakrishna, Harish

2016-10-01

The surgical and procedural specialties are continually evolving their methods to include more complex and technically difficult cases. These cases can be longer and incorporate multiple teams in a different model of operating room synergy. Patients are frequently older, with comorbidities adding to the complexity of these cases. Recording of this environment has become more feasible recently with advancement in video and audio capture systems often used in the simulation realm. We began using live capture to record a new procedure shortly after starting these cases in our institution. This has provided continued assessment and evaluation of live procedures. The goal of this was to improve human factors and situational challenges by review and debriefing. B-Line Medical's LiveCapture video system was used to record successive transcatheter aortic valve replacement (TAVR) procedures in our cardiac catheterization/laboratory. An illustrative case is used to discuss analysis and debriefing of the case using this system. An illustrative case is presented that resulted in long-term changes to our approach of these cases. The video capture documented rare events during one of our TAVR procedures. Analysis and debriefing led to definitive changes in our practice. While there are hurdles to the use of this technology in every institution, the role for the ongoing use of video capture, analysis, and debriefing may play an important role in the future of patient safety and human factors analysis in the operating environment.

The utility of live video capture to enhance debriefing following transcatheter aortic valve replacement

PubMed Central

Seamans, David P.; Louka, Boshra F.; Fortuin, F. David; Patel, Bhavesh M.; Sweeney, John P.; Lanza, Louis A.; DeValeria, Patrick A.; Ezrre, Kim M.; Ramakrishna, Harish

2016-01-01

Background: The surgical and procedural specialties are continually evolving their methods to include more complex and technically difficult cases. These cases can be longer and incorporate multiple teams in a different model of operating room synergy. Patients are frequently older, with comorbidities adding to the complexity of these cases. Recording of this environment has become more feasible recently with advancement in video and audio capture systems often used in the simulation realm. Aims: We began using live capture to record a new procedure shortly after starting these cases in our institution. This has provided continued assessment and evaluation of live procedures. The goal of this was to improve human factors and situational challenges by review and debriefing. Setting and Design: B-Line Medical's LiveCapture video system was used to record successive transcatheter aortic valve replacement (TAVR) procedures in our cardiac catheterization/laboratory. An illustrative case is used to discuss analysis and debriefing of the case using this system. Results and Conclusions: An illustrative case is presented that resulted in long-term changes to our approach of these cases. The video capture documented rare events during one of our TAVR procedures. Analysis and debriefing led to definitive changes in our practice. While there are hurdles to the use of this technology in every institution, the role for the ongoing use of video capture, analysis, and debriefing may play an important role in the future of patient safety and human factors analysis in the operating environment. PMID:27762242

Aortic valve dysfunction and aortic dilation in adults with coarctation of the aorta.

PubMed

Clair, Mathieu; Fernandes, Susan M; Khairy, Paul; Graham, Dionne A; Krieger, Eric V; Opotowsky, Alexander R; Singh, Michael N; Colan, Steven D; Meijboom, Erik J; Landzberg, Michael J

2014-01-01

To determine the prevalence of aortic valve dysfunction, aortic dilation, and aortic valve and ascending aortic intervention in adults with coarctation of the aorta (CoA). Aortic valve dysfunction and aortic dilation are rare among children and adolescents with CoA. With longer follow-up, adults may be more likely to have progressive disease. We retrospectively reviewed all adults with CoA, repaired or unrepaired, seen at our center between 2004 and 2010. Two hundred sixteen adults (56.0% male) with CoA were identified. Median age at last evaluation was 28.3 (range 18.0 to 75.3) years. Bicuspid aortic valve (BAV) was present in 65.7%. At last follow-up, 3.2% had moderate or severe aortic stenosis, and 3.7% had moderate or severe aortic regurgitation. Dilation of the aortic root or ascending aorta was present in 28.0% and 41.6% of patients, respectively. Moderate or severe aortic root or ascending aortic dilation (z-score > 4) was present in 8.2% and 13.7%, respectively. Patients with BAV were more likely to have moderate or severe ascending aortic dilation compared with those without BAV (19.5% vs. 0%; P < 0.001). Age was associated with ascending aortic dilation (P = 0.04). At most recent follow-up, 5.6% had undergone aortic valve intervention, and 3.2% had aortic root or ascending aortic replacement. In adults with CoA, significant aortic valve dysfunction and interventions during early adulthood were uncommon. However, aortic dilation was prevalent, especially of the ascending aorta, in patients with BAV. © 2013 Wiley Periodicals, Inc.

A small case series of aortic balloon occlusion in trauma: lessons learned from its use in ruptured abdominal aortic aneurysms and a brief review.

PubMed

Hörer, T M; Skoog, P; Pirouzram, A; Nilsson, K F; Larzon, T

2016-10-01

EndoVascular and Hybrid Trauma Management (EVTM) is an emerging concept for the early treatment of trauma patients using aortic balloon occlusion (ABO), embolization agents and stent grafts to stop ongoing traumatic bleeding. These techniques have previously been implemented successfully in the treatment of ruptured aortic aneurysm. We describe our very recent experience of EVTM using ABO in bleeding patients and lessons learned over the last 20 years from the endovascular treatment of ruptured abdominal aortic aneurysms (rAAA). We also briefly describe current knowledge of ABO usage in trauma. A small series of educational cases in our hospital is described, where endovascular techniques were used to gain temporary hemorrhage control. The methods used for rAAA and their applicability to EVTM with a multidisciplinary approach are presented. Establishing femoral arterial access immediately on arrival at the emergency room and use of an angiography table in the surgical suite may facilitate EVTM at an early stage. ABO may be an effective method for the temporary stabilization of severely hemodynamically unstable patients with hemorrhagic shock, and may be useful as a bridge to definitive treatment of the bleeding patients. EVTM, including the usage of ABO, can be initiated on patient arrival and is feasible. Further data need to be collected to investigate proper indications for ABO, best clinical usage, results and potential complications. Accordingly, the ABOTrauma Registry has recently been set up. Existing experiences of EVTM and lessons from the endovascular treatment of rAAA may be useful in trauma management.

Hypercholesterolemia potentiates aortic endothelial response to inhaled diesel exhaust

PubMed Central

Maresh, J. Gregory; Campen, Matthew J.; Reed, Matthew D.; Darrow, April L.; Shohet, Ralph V.

2012-01-01

Background Inhalation of diesel exhaust induces vascular effects including impaired endothelial function and increased atherosclerosis. Objective To examine the in vivo effects of subchronic diesel exhaust exposure on endothelial cell transcriptional responses in the presence of hypercholesterolemia. Methods ApoE (−/−) and ApoE (+/+) mice inhaled diesel exhaust diluted to particulate matter levels of 300 or 1000 μg/m3 vs. filtered air. After 30 days, endothelial cells were harvested from dispersed aortic cells by fluorescent-activated cell sorting (FACS). Relative mRNA abundance was evaluated by microarray analysis to measure strain-specific transcriptional responses in mice exposed to dilute diesel exhaust vs. filtered air. Results Forty-nine transcripts were significantly dysregulated by >2.8-fold in the endothelium of ApoE (−/−) mice receiving diesel exhaust at 300 or 1000 μg/m3. These included transcripts with roles in plasminogen activation, endothelial permeability, inflammation, genomic stability, and atherosclerosis; similar responses were not observed in ApoE (+/+) mice. Conclusions The potentiation of diesel exhaust-related endothelial gene regulation by hypercholesterolemia helps to explain air pollution-induced vascular effects in animals and humans. The observed regulated transcripts implicate pathways important in the acceleration of atherosclerosis by air pollution. PMID:21222557

Invasion of human aortic endothelial cells by oral viridans group streptococci and induction of inflammatory cytokine production.

PubMed

Nagata, E; de Toledo, A; Oho, T

2011-02-01

Oral viridans group streptococci are the major commensal bacteria of the supragingival oral biofilm and have been detected in human atheromatous plaque. Atherosclerosis involves an ongoing inflammatory response, reportedly involving chronic infection caused by multiple pathogens. The aim of this study was to examine the invasion of human aortic endothelial cells (HAECs) by oral viridans group streptococci and the subsequent cytokine production by viable invaded HAECs. The invasion of HAECs by bacteria was examined using antibiotic protection assays and was visualized by confocal scanning laser microscopy. The inhibitory effects of catalase and cytochalasin D on the invasion of HAECs were also examined. The production of cytokines by invaded or infected HAECs was determined using enzyme-linked immunosorbent assays, and a real-time polymerase chain reaction method was used to evaluate the expression of cytokine messenger RNA. The oral streptococci tested were capable of invading HAECs. The number of invasive bacteria increased with the length of the co-culture period. After a certain co-culture period, some organisms were cytotoxic to the HAECs. Catalase and cytochalasin D inhibited the invasion of HAECs by the organism. HAECs invaded by Streptococcus mutans Xc, Streptococcus gordonii DL1 (Challis), Streptococcus gordonii ATCC 10558 and Streptococcus salivarius ATCC 13419 produced more cytokine(s) (interleukin-6, interleukin-8, monocyte chemoattractant protein-1) than non-invaded HAECs. The HAECs invaded by S. mutans Xc produced the largest amounts of cytokines, and the messenger RNA expression of cytokines by invaded HAECs increased markedly compared with that by non-invaded HAECs. These results suggest that oral streptococci may participate in the pathogenesis of atherosclerosis. © 2010 John Wiley & Sons A/S.

Lessons on the pathogenesis of aneurysm from heritable conditions

PubMed Central

Lindsay, Mark E.; Dietz, Harry C.

2013-01-01

Aortic aneurysm is common, accounting for 1–2% of all deaths in industrialized countries. Early theories of the causes of human aneurysm mostly focused on inherited or acquired defects in components of the extracellular matrix in the aorta. Although several mutations in the genes encoding extracellular matrix proteins have been recognized, more recent discoveries have shown important perturbations in cytokine signalling cascades and intracellular components of the smooth muscle contractile apparatus. The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-β cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies. PMID:21593863

Echocardiography as a Predicting Method in Diagnosis, Evaluation and Assessment of Children with Subvalvar Aortic Stenosis

PubMed Central

Bejiqi, Ramush; Bejiqi, Hana; Retkoceri, Ragip

2016-01-01

BACKGROUND: Obstruction to the left ventricular outflow of the heart may be above the aortic valve (5%), at the valve (74%), or in the subvalvar region (23%). These anomalies represent 3 to 6% of all patients with congenital heart defects (CHD), and it occurs more often in males (male-female ratio of 4:1). AIM: The purpose of this study was to determine the sensitivity and specificity of transthoracic echocardiography in diagnosis of discrete subaortic membrane, to determine convenient time for surgical intervention, and for identifying involvement of the aortic valve by subaortic shelf. MATERIAL AND METHODS: A retrospective review of the medical records and echocardiograms of 18 patients [14 male (77%) and 4 female (23%)] with discrete subaortic membrane, aged 11 month to 12 years, with mean age of 5 years and 3 month, diagnosed at the Pediatric Clinic in Prishtina, during the period September, 1999 and December, 2010 were done. RESULTS: Four patients, in neonatal age were operated from critical coarctation of the aorta and, initial signs of congestive heart failure were presented. 2 of them were operated in Belgrade, Serbia and 2 in Lausanne, Switzerland. CONCLUSION: In all presented patients bicuspid aortic valve was noted, but none of them subaortic membrane was registered. PMID:27275334

Evaluation of Acute Aortic Dissection Type a Factors and Comparison the Postoperative Clinical Outcomes between Two Surgical Methods.

PubMed

Shemirani, Hasan; Mirmohamadsadeghi, Amir; Mahaki, Behzad; Farhadi, Sadaf; Badalabadi, Reza Mohseni; Bidram, Peyman; Badalabadi, Mehdi Mohseni

2017-01-01

Although aortic dissection is a rare disease, it causes high level of mortality. If ascending aorta gets involved in this disease, it is known as type A. According to small number of studies about this disease in Iran, this study conducted to detect the factors related to acute aortic dissection type A, its surgery consequences and the factors affecting them. In this historical cohort study, all patients having acute aortic dissection type A referring to Chamran Hospital from 2006 to 2012 were studied. The impact of two surgical methods including antegrade cerebral perfusion (ACP) and retrograde cerebral one (RCP) on surgical and long-term mortality and recurrence of dissection was determined. The relation of mortality rate and hemodynamic instability before surgery, age more than 70 years old, ejection fraction lower than 50%, prolonged cardiopulmonary bypass pump (CPBP) time and excessive blood transfusion, was assessed. Surgery and long-term mortality and recurrence of dissection were 35.3%, 30.8% and 30.4%. Surgical and long-term death in the patients being operated by ACP method was lower than those one being operated by RCP ( P < 0.001). Excessive blood transfusion and unstable hemodynamic condition had significant effect on surgical mortality ( P = 0.014, 0.030, respectively). CPBP time and unstable hemodynamic condition affected long-term mortality significantly ( P = 0.002). The result found that ACP is the preferable kind of surgery in comparison with RCP according to the surgical and long-term mortality.

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta

PubMed Central

Rueda-Martínez, Carmen; Lamas, Oscar; Mataró, María José; Robledo-Carmona, Juan; Sánchez-Espín, Gemma; Jiménez-Navarro, Manuel; Such-Martínez, Miguel; Fernández, Borja

2014-01-01

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples. PMID:24841551

[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].

PubMed

Sievers, Hans H

2002-08-01

At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially if these are progressive and combined with aortic insufficiency. ROSS-OPERATION: The Ross-Operation includes the replacement of the diseased aortic valve with the pulmonary autograft and reconstruction of the right ventricular outflow tract using a homograft. The hemodynamic results are excellent regarding the autograft and also the clinical results with very low thromboembolic risk and acceptable reoperation rate. This method is especially indicated for active young patients, women, who desire children, athletes and patients in general, who like to avoid long-term anticoagulation. In some cases the homograft may develop a dysfunction predominantly a pulmonary stenosis requiring reoperation. In the author's series of 245 Ross-operations in 12 years the homograft had to be replaced in 4 cases without letality. Innovative, decellularized homografts with the potential to repopulate with autologeous cells show promising results after 1 year of clinical implantation without signs of antibody development. Probably these tissue-engineered modification may improve the homograft results. The reconstructive techniques of the aortic valve and the Ross-operation have a certain risk of reoperation that must be weighed against the advantages of very low hospital and late valve related death, excellent hemodynamics, very low risk of macro- and microembolism as well as bleeding, lack of long-term anticoagulation and unrestricted life-style.

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

PubMed

Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Comment to 'Regarding "Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms"'.

PubMed

Wierzba, Waldemar; Sliwczynski, Andrzej; Pinkas, Jaroslaw; Jawien, Arkadiusz; Karnafel, Waldemar

2018-01-01

This publication is a commentary on the Letter to the Editor by Juliette Raffort and Fabien Lareyre. This article clarifies a number of concerns about the method of calculating the index of prevalence of ruptured abdominal aortic aneurysms (AAA). The method of qualifying patients for the study and the method of calculating the index of prevalence of ruptured AAA in cohorts of diabetic and non-diabetic patients was presented. Most researchers calculate the Index of Prevalence per 100,000 of the general population. This gives the misleading result that diabetes reduces the risk of AAA rupture.We used a method which calculated prevalence per 100,000 with diabetes mellitus and per 100,000 without diabetes mellitus. This method confirms that diabetes mellitus increases the risk of ruptured AAA.

Immersed boundary peridynamics (IB/PD) method to simulate aortic dissection

NASA Astrophysics Data System (ADS)

Bhalla, Amneet Pal Singh; Griffith, Boyce

2016-11-01

Aortic dissection occurs when an intimal tear in the aortic wall propagates into the media to form a false lumen within the vessel wall. Rupture of the false lumen and collapse of the true lumen both carry a high risk of morbidity and mortality. Surgical treatment consists of either replacement of a portion of the aorta, or stent implantation to cover the affected segment. Both approaches carry significant risks: open surgical intervention is highly invasive, whereas stents can be challenging to implant and offer unclear long-term patient outcomes. It is also difficult to time optimally the intervention to ensure that the benefits of treatment outweigh its risks. In this work we develop innovative fluid-structure interaction (FSI) model combining elements from immersed boundary (IB) and peridynamics (PD) methods to simulate tears in membranes. The new approach is termed as IB/PD method. We use non-ordinary state based PD to represent material hyperelasticity. Several test problems are taken to validate peridynamics approach to model structural dynamics, with and without accounting for failure in the structures. FSI simulations using IB/PD method are compared with immersed finite element method (IB/FE) to validate the new hybrid approach. NIH Award R01HL117163 NSF Award ACI 1450327.

Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis.

PubMed

Didangelos, Athanasios; Mayr, Ursula; Monaco, Claudia; Mayr, Manuel

2012-06-01

Atherosclerosis is initiated by the retention of lipoproteins on proteoglycans in the arterial intima. However, the mechanisms leading to proteoglycan accumulation and lipoprotein retention are poorly understood. In this study, we set out to investigate the role of ADAMTS-5 (a disintegrin and metalloprotease with thrombospondin motifs-5) in the vasculature. ADAMTS-5 was markedly reduced in atherosclerotic aortas of apolipoprotein E-null (apoE(-/-)) mice. The reduction of ADAMTS-5 was accompanied by accumulation of biglycan and versican, the major lipoprotein-binding proteoglycans, in atherosclerosis. ADAMTS-5 activity induced the release of ADAMTS-specific versican (DPEAAE(441)) and aggrecan ((374)ALGS) fragments as well as biglycan and link protein from the aortic wall. Fibroblast growth factor 2 (FGF-2) inhibited ADAMTS-5 expression in isolated aortic smooth muscle cells and blocked the spontaneous release of ADAMTS-generated versican and aggrecan fragments from aortic explants. In aortas of ADAMTS-5-deficient mice, DPEAAE(441) versican neoepitopes were not detectable. Instead, biglycan levels were increased, highlighting the role of ADAMTS-5 in the catabolism of vascular proteoglycans. Importantly, ADAMTS-5 proteolytic activity reduced the LDL binding ability of biglycan and released LDL from human aortic lesions. This study provides the first evidence implicating ADAMTS-5 in the regulation of proteoglycan turnover and lipoprotein retention in atherosclerosis.

Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation

PubMed Central

Valente, Acrisio Sales; Alencar, Polyanna; Santos, Alana Neiva; Lobo, Roberto Augusto de Mesquita; de Mesquita, Fernando Antônio; Guimarães, Aloyra Guedis

2013-01-01

The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course. PMID:24598962

Minimally Invasive Aortic Valve Replacement Following Root Enlargement on too Narrow Annulus to Perform Transcatheter Aortic Valve Implantation.

PubMed

Sakamoto, Kosuke; Totsugawa, Toshinori; Hiraoka, Arudo; Tamura, Kentaro; Yoshitaka, Hidenori; Sakaguchi, Taichi

2018-05-30

An 88-year-old woman was diagnosed with aortic stenosis and an aortic annulus that was too narrow to perform transcatheter aortic valve implantation. Surgery was performed through a 7-cm right mini-thoracotomy at the fourth intercostal space. A 19-mm aortic valve bioprosthesis was implanted after root enlargement. The fourth intercostal space was a suitable site for aortic root enlargement because of the shorter skin-to-root distance and the detailed exposure of the aortic valve after cutting the aortic wall. This study concluded that minimally-invasive aortic valve replacement following root enlargement can be an option for the treatment of elderly patients with aortic stenosis accompanied by an annulus that is too small to perform transcatheter aortic valve implantation.

Fenestrated and Chimney Technique for Juxtarenal Aortic Aneurysm: A Systematic Review and Pooled Data Analysis

PubMed Central

Li, Yue; Hu, Zhongzhou; Bai, Chujie; Liu, Jie; Zhang, Tao; Ge, Yangyang; Luan, Shaoliang; Guo, Wei

2016-01-01

Juxtarenal aortic aneurysms (JAA) account for approximately 15% of abdominal aortic aneurysms. Fenestrated endovascular aneurysm repair (FEVAR) and chimney endovascular aneurysm repair (CH-EVAR) are both effective methods to treat JAAs, but the comparative effectiveness of these treatment modalities is unclear. We searched the PubMed, Medline, Embase, and Cochrane databases to identify English language articles published between January 2005 and September 2013 on management of JAA with fenestrated and chimney techniques to conduct a systematic review to compare outcomes of patients with juxtarenal aortic aneurysm (JAA) treated with the two techniques. We compared nine F-EVAR cohort studies including 542 JAA patients and 8 CH-EVAR cohorts with 158 JAA patients regarding techniques success rates, 30-day mortality, late mortality, endoleak events and secondary intervention rates. The results of this systematic review indicate that both fenestrated and chimney techniques are attractive options for JAAs treatment with encouraging early and mid-term outcomes. PMID:26869488

Bicuspid Aortic Valve

DTIC Science & Technology

2006-08-01

severe aortic stenosis . Figure 1F. Oblique axial cine bright blood imaging through the valve plane of the aorta, demonstrates the aortic valve to...the ascending aorta. This moderate to large jet is consistent with moderate to severe aortic stenosis . No diastolic jet to suggest aortic ...conditions. Functional impairment of the aortic valve—namely aortic stenosis and aortic regurgitation—is the most common complication (in up to 68-85% of

3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement.

PubMed

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K; Goncalves, Alexandra; Di Carli, Marcelo F; Rybicki, Frank J; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2016-01-01

3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of -0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Mortality characteristics of aortic root surgery in North America†

PubMed Central

Caceres, Manuel; Ma, Yicheng; Rankin, J. Scott; Saha-Chaudhuri, Paramita; Englum, Brian R.; Gammie, James S.; Suri, Rakesh M.; Thourani, Vinod H.; Esmailian, Fardad; Czer, Lawrence S.; Puskas, John D.; Svensson, Lars G.

2014-01-01

OBJECTIVES Aortic root surgery is transitioning to aortic valve sparing (AVS), but little is known about the relative early outcomes of AVS versus composite graft-valve replacement (CVR). This study assessed mortality differences for AVS versus CVR to guide future practice decisions. METHODS From January 2000 to June 2011, 31 747 patients had aortic root replacement with AVS (n = 3585; 11%) or CVR (n = 28 162; 89%). The cohort of Overall patients was divided into two subgroups: high-risk patients (n = 20 356; 6% AVS) having age >75 years, endocarditis, aortic stenosis, dialysis, multiple valves, reoperation or emergency/salvage status, and the remaining low-risk patients (n = 11 388; 21% AVS). Using logistic regression analysis, outcomes were presented as unadjusted operative mortality (UOM), risk-adjusted operative mortality (AOM) and adjusted odds ratio (AOR) for mortality. RESULTS Baseline characteristics for the Overall group (AVS versus CVR) were: mean age (52 vs 57 years), endocarditis (1 vs 11%), aortic stenosis (4 vs 36%), dialysis (1 vs 2%), multiple valves (7 vs 10%), reoperation (6 vs 17%) and emergency status (14 vs 12%) (all P < 0.0001). In high- and low-risk groups, baseline differences narrowed, and lower mortality was generally observed with AVS: (AVS versus CVR) UOM group Overall (4.5 vs 8.9%)*, group High-risk (10.5 vs 11.7%), group Low-risk (1.4 vs 3.1%)*; AOM group Overall (6.2 vs 8.6%), group High-risk (10.1 vs 11.7%), group Low-risk (2.2 vs 2.8%); AOR group Overall (0.59)*, group High-risk (0.62)*, group Low-risk (0.69). *P < 0.05. CONCLUSIONS Relative risk-adjusted mortality seemed comparable with AVS versus CVR in low- and high-risk subgroups. These data support judicious expansion of aortic valve repair in patients having aortic root replacement. PMID:24639452

Temporal variability of vena contracta and jet areas with color Doppler in aortic regurgitation: a chronic animal model study.

PubMed

Ishii, M; Jones, M; Shiota, T; Yamada, I; Sinclair, B; Heinrich, R S; Yoganathan, A P; Sahn, D J

1998-11-01

The purpose of our study was to determine the temporal variability of regurgitant color Doppler jet areas and the width of the color Doppler imaged vena contracta for evaluating the severity of aortic regurgitation. Twenty-nine hemodynamically different states were obtained pharmacologically in 8 sheep 20 weeks after surgery to produce aortic regurgitation. Aortic regurgitation was quantified by peak and mean regurgitant flow rates, regurgitant stroke volumes, and regurgitant fractions determined using pulmonary and aortic electromagnetic flow probes and meters balanced against each other. The regurgitant jet areas and the widths of color Doppler imaged vena contracta were measured at 4 different times during diastole to determine the temporal variability of this parameter. When measured at 4 different temporal points in diastole, a significant change was observed in the size of the color Doppler imaged regurgitant jet (percent of difference: from 31.1% to 904%; 233% +/- 245%). Simple linear regression analysis between each color jet area at 4 different periods in diastole and flow meter-based severity of the aortic regurgitation showed only weak correlation (0.23 < r < 0.49). In contrast, for most conditions only a slight change was observed in the width of the color Doppler imaged vena contracta during the diastolic regurgitant period (percent of difference, vena contracta: from 2.4% to 12.9%, 5.8% +/- 3.2%). In addition, for each period the width of the color Doppler imaged vena contracta at the 4 different time periods in diastole correlated quite strongly with volumetric measures of the severity of aortic regurgitation (0.81 < r < 0.90) and with the instantaneous flow rate for the corresponding period (0.85 < r < 0.87). Color Doppler imaged vena contracta may provide a simple, practical, and accurate method for quantifying aortic regurgitation, even when using a single frame color Doppler flow mapping image.

Post-exercise effects on aortic wave reflection derived from wave separation analysis in young- to middle-aged pre-hypertensives and hypertensives.

PubMed

Millen, Aletta M E; Woodiwiss, Angela J; Norton, Gavin R

2016-07-01

Decreases in brachial blood pressure (BP) may occur for several hours following a bout of exercise. Although aortic backward waves predict cardiovascular damage independent of brachial BP, whether decreases in aortic backward waves also occur post-exercise in young-to-middle-aged hypertensives, the extent to which these changes exceed brachial BP changes, and the best method of identifying these changes is uncertain. We examined aortic function at baseline and 15-min post-exercise in 20 pre-hypertensive or hypertensive men and women (age 45 ± 7 years). Central aortic pressure, forward (Pf) and backward (Pb) wave pressures, the reflection index (RI) and augmentation pressure (AP) and index (AIx) were determined using applanation tonometry, and SphygmoCor software. Decreases in central aortic (p < 0.001) but not brachial systolic BP and pulse pressure (PP) occurred post-exercise. In addition, decreases in post-exercise (baseline versus post-exercise) Pb (19 ± 4 vs 13 ± 3 mm Hg p < 0.0001), RI (72.9 ± 22.1 vs 47.6 ± 12.8 %, p < 0.0001), AIx (26.3 ± 10.8 vs 7.8 ± 11.6 %, p < 0.0001) and AP (9.9 ± 3.9 vs 2.8 ± 3.9 mm Hg, p < 0.0001), but not Pf, were noted. However, decreases in AIx were not correlated with decreases in Pb, and whilst decreases in aortic PP correlated with decreases in Pb (p < 0.0001), no correlations were noted with decreases in AP or AIx. In young-to-middle-aged pre-hypertensive and hypertensive individuals, aortic backward waves decrease post-exercise; this change is not reflected in brachial BP measurements and is poorly indexed by measures of pressure augmentation.

Evaluation of aortic valve stenosis using cardiovascular magnetic resonance: comparison of an original semiautomated analysis of phase-contrast cardiovascular magnetic resonance with Doppler echocardiography.

PubMed

Defrance, Carine; Bollache, Emilie; Kachenoura, Nadjia; Perdrix, Ludivine; Hrynchyshyn, Nataliya; Bruguière, Eric; Redheuil, Alban; Diebold, Benoit; Mousseaux, Elie

2012-09-01

Accurate quantification of aortic valve stenosis (AVS) is needed for relevant management decisions. However, transthoracic Doppler echocardiography (TTE) remains inconclusive in a significant number of patients. Previous studies demonstrated the usefulness of phase-contrast cardiovascular magnetic resonance (PC-CMR) in noninvasive AVS evaluation. We hypothesized that semiautomated analysis of aortic hemodynamics from PC-CMR might provide reproducible and accurate evaluation of aortic valve area (AVA), aortic velocities, and gradients in agreement with TTE. We studied 53 AVS patients (AVA(TTE)=0.87±0.44 cm(2)) and 21 controls (AVA(TTE)=2.96±0.59 cm(2)) who had TTE and PC-CMR of aortic valve and left ventricular outflow tract on the same day. PC-CMR data analysis included left ventricular outflow tract and aortic valve segmentation, and extraction of velocities, gradients, and flow rates. Three AVA measures were performed: AVA(CMR1) based on Hakki formula, AVA(CMR2) based on continuity equation, AVA(CMR3) simplified continuity equation=left ventricular outflow tract peak flow rate/aortic peak velocity. Our analysis was reproducible, as reflected by low interoperator variability (<4.56±4.40%). Comparison of PC-CMR and TTE aortic peak velocities and mean gradients resulted in good agreement (r=0.92 with mean bias=-29±62 cm/s and r=0.86 with mean bias=-12±15 mm Hg, respectively). Although good agreement was found between TTE and continuity equation-based CMR-AVA (r>0.94 and mean bias=-0.01±0.38 cm(2) for AVA(CMR2), -0.09±0.28 cm(2) for AVA(CMR3)), AVA(CMR1) values were lower than AVA(TTE) especially for higher AVA (mean bias=-0.45±0.52 cm(2)). Besides, ability of PC-CMR to detect severe AVS, defined by TTE, provided the best results for continuity equation-based methods (accuracy >94%). Our PC-CMR semiautomated AVS evaluation provided reproducible measurements that accurately detected severe AVS and were in good agreement with TTE.

Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions

NASA Astrophysics Data System (ADS)

Lee, Phin Peng

Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated 'pro-healing' properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

Bicuspid aortic valves: diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT.

PubMed

Murphy, David J; McEvoy, Sinead H; Iyengar, Sri; Feuchtner, Gudrun; Cury, Ricardo C; Roobottom, Carl; Baumueller, Stephan; Alkadhi, Hatem; Dodd, Jonathan D

2014-08-01

To assess the diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT for bicuspid aortic valves. The standard axial chest CT scans of 20 patients with known bicuspid aortic valves were blindly, randomly analyzed for (i) the appearance of the valve cusps, (ii) the largest aortic sinus area, (iii) the longest aortic cusp length, (iv) the thickest aortic valve cusp and (v) valve calcification. A second blinded reader independently analyzed the appearance of the valve cusps. Forty-two age- and sex-matched patients with known tricuspid aortic valves were used as controls. Retrospectively ECG-gated cardiac CT multiphase reconstructions of the aortic valve were used as the gold-standard. Fourteen (21%) scans were scored as unevaluable (7 bicuspid, 7 tricuspid). Of the remainder, there were 13 evaluable bicuspid valves, ten of which showed an aortic valve line sign, while the remaining three showed a normal Mercedes-Benz appearance owing to fused valve cusps. The 35 evaluable tricuspid aortic valves all showed a normal Mercedes-Benz appearance (P=0.001). Kappa analysis=0.62 indicating good interobserver agreement for the aortic valve cusp appearance. Aortic sinus areas, aortic cusp lengths and aortic cusp thicknesses of ≥ 3.8 cm(2), 3.2 cm and 1.6mm respectively on standard axial chest CT best distinguished bicuspid from tricuspid aortic valves (P<0.0001 for all). Of evaluable scans, the sensitivity, specificity, positive and negative predictive values of standard axial chest CT in diagnosing bicuspid aortic valves was 77% (CI 0.54-1.0), 100%, 100% and 70% respectively. The aortic valve is evaluable in approximately 80% of standard chest 64-slice CT scans. Bicuspid aortic valves may be diagnosed on evaluable scans with good diagnostic accuracy. An aortic valve line sign, enlarged aortic sinuses and elongated, thickened valve cusps are specific CT features. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling

PubMed Central

von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

2016-01-01

Background Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. Study aim was to describe blood flow patterns in the ascending aorta of AS patients and determine their association with remodeling. Methods and Results Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age 63±13 years) and 37 healthy controls (age 60±10 years) underwent 4D-flow MRI. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress (WSSpeak) in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index (LVMI-I) and the ratio of LV mass to enddiastolic volume (relative wall mass; RWM). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and AS patients exhibited an asymmetric and elevated distribution of WSSpeak. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (p=0.0274), eccentricity (p=0.0070) and flow displacement (p=0.0021). Bicuspid aortic valve was associated with more intense helical (p=0.0098) and vortical flow formation (p=0.0536), higher flow displacement (p=0.11) and higher WSSpeak (p=0.0926). LVM-I and RWM were significantly associated with aortic orifice area (p=0.0611, p=0.0058) and flow displacement (p=0.0058, p=0.0283). Conclusions In this pilot study, AS leads to abnormal blood flow pattern and WSSpeak in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. PMID:26917824

Brief group training of medical students in focused cardiac ultrasound may improve diagnostic accuracy of physical examination.

PubMed

Stokke, Thomas M; Ruddox, Vidar; Sarvari, Sebastian I; Otterstad, Jan E; Aune, Erlend; Edvardsen, Thor

2014-11-01

Physical examination and auscultation can be challenging for medical students. The aim of this study was to investigate whether a brief session of group training in focused cardiac ultrasound (FCU) with a pocket-sized device would allow medical students to improve their ability to detect clinically relevant cardiac lesions at the bedside. Twenty-one medical students in their clinical curriculum completed 4 hours of FCU training in groups. The students examined patients referred for echocardiography with emphasis on auscultation, followed by FCU. Findings from physical examination and FCU were compared with those from standard echocardiography performed and analyzed by cardiologists. In total, 72 patients were included in the study, and 110 examinations were performed. With a stethoscope, sensitivity to detect clinically relevant (moderate or greater) valvular disease was 29% for mitral regurgitation, 33% for aortic regurgitation, and 67% for aortic stenosis. FCU improved sensitivity to detect mitral regurgitation (69%, P < .001). However, sensitivity to detect aortic regurgitation (43%) and aortic stenosis (70%) did not improve significantly. Specificity was ≥89% for all valvular diagnoses by both methods. For nonvalvular diagnoses, FCU's sensitivity to detect moderate or greater left ventricular dysfunction (90%) was excellent, detection of right ventricular dysfunction (79%) was good, while detection of dilated left atrium (53%), dilated right atrium (49%), pericardial effusion (40%), and dilated aortic root (25%) was less accurate. Specificity varied from 57% to 94%. After brief group training in FCU, medical students could detect mitral regurgitation significantly better compared with physical examination, whereas detection of aortic regurgitation and aortic stenosis did not improve. Left ventricular dysfunction was detected with high sensitivity. More extensive training is advised. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Endovascular Repair of Traumatic Rupture of the Thoracic Aorta: Single-Center Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saratzis, Nikolaos A., E-mail: saratzis@germanosnet.gr; Saratzis, Athanasios N.; Melas, Nikolaos

Purpose. Traumatic rupture of the thoracic aorta secondary to blunt chest trauma is a life-threatening emergency and a common cause of death, usually following violent collisions. The objective of this retrospective report was to evaluate the efficacy of endovascular treatment of thoracic aortic disruptions with a single commercially available stent-graft. Methods. Nine men (mean age 29.5 years) were admitted to our institution between January 2003 and January 2006 due to blunt aortic trauma following violent motor vehicle collisions. Plain chest radiography, spiral computed tomography, aortography, and transesophageal echocardiography were used for diagnostic purposes in all cases. All patients were diagnosedmore » with contained extramural thoracic aortic hematomas, secondary to aortic disruption. One patient was also diagnosed with a traumatic thoracic aortic dissection, secondary to blunt trauma. All subjects were poor surgical candidates, due to major injuries such as multiple bone fractures, abdominal hematomas, and pulmonary contusions. All repairs were performed using the EndoFit (LeMaitre Vascular) stent-graft. Results. Complete exclusion of the traumatic aortic disruption and pseudoaneurysm was achieved and verified at intraoperative arteriography and on CT scans, within 10 days of the repair in all patients. In 1 case the deployment of a second cuff was necessary due to a secondary endoleak. In 2 cases the left subclavian artery was occluded to achieve adequate graft fixation. No procedure-related deaths have occurred and no cardiac or peripheral vascular complications were observed within the 12 months (range 8-16 months) follow-up. Conclusions. This is the first time the EndoFit graft has been utilized in the treatment of thoracic aortic disruptions secondary to chest trauma. The repair of such pathologies is technically feasible and early follow-up results are promising.« less

Novel intravascular ultrasound-guided method to create transintimal arterial communications: initial experience in peripheral occlusive disease and aortic dissection.

PubMed

Saket, Ramin R; Razavi, Mahmood K; Padidar, Arash; Kee, Stephen T; Sze, Daniel Y; Dake, Michael D

2004-06-01

To report our experience using a commercially available catheter-based system equipped with an intravascular ultrasound (IVUS) transducer to achieve controlled true lumen re-entry in patients undergoing subintimal angioplasty for chronic total occlusions (CTO) or aortic dissections. During an 8-month period, 10 patients (6 men; mean age 73.4 years) with lower extremity (LE) ischemia from CTOs (n=7) or true lumen collapse from aortic dissections (n=3) were treated. Subintimal access and controlled re-entry of the CTOs were performed with a commercially available 6.2-F dual-lumen catheter, which contained an integrated 64-element phased-array IVUS transducer and a deployable 24-G needle through which a guidewire was passed once the target lumen was reached. The occluded segments were balloon dilated; self-expanding nitinol stents were deployed. In the aortic dissections, fenestrations were performed using the same device, with the IVUS unit acting as the guide. The fenestrations were balloon dilated and stented to support the true lumen. Time to effective re-entry ranged from 6 to 10 minutes (mean 7) in the CTOs; antegrade flow was restored in all 7 CTOs, and the patients were free of ischemic symptoms at up to 8-month follow-up. In the aortic dissection cases, the fenestrations equalized pressures between the lumens and restored flow into the compromised vessels. There were no complications related to the use of this device in any of the 10 patients. Our preliminary results demonstrate the feasibility of using this catheter-based system for subintimal recanalization with controlled re-entry in CTOs and for aortic flap fenestrations in aortic dissections. This approach can improve the technical success rate, reduce the time of the procedure, and minimize potential complications.

Endovascular repair of thoracic aortic traumatic transections is a safe method in patients with complicated injuries.

PubMed

Rahimi, Saum A; Darling, R Clement; Mehta, Manish; Roddy, Sean P; Taggert, John B; Sternbach, Yaron

2010-10-01

Historically thoracic aortic rupture secondary to trauma was treated with cardiopulmonary bypass and open surgery. With the advent of endovascular grafting, physicians have the ability to reconstruct the thoracic aortic transection using a less invasive technique. In this study, we examine our experience with stent graft repair of thoracic transections secondary to trauma. The medical records of patients treated at a level I trauma center from 2005 to 2008 were reviewed. Those patients who had an aortic transection treated with an endograft were identified and evaluated for in-hospital mortality and morbidity and concurrent injuries. Demographics, procedural details, and outcomes were analyzed. Over a 3-year period, 18 thoracic aortic transections secondary to trauma were identified in patients with a mean age of 43 (range, 16-80). Primary technical success was 100%. None of the patients required explant or open repair during this time period. In-hospital mortality was 2 of 18 (11%); all patients had multiple trauma including long bone fractures. The subclavian artery origin was covered by the stent graft in 9 of the 18 patients. The mean estimated blood loss per procedure was 222 cc. No patient in this series had postoperative paraplegia. Follow-up ranged from 1 to 50 months with an average of 13 months. There have been no late explantation or device failures identified. Endovascular repair of traumatic thoracic aortic transections can be performed safely with a relatively low mortality and morbidity and should be the procedure of choice for patients presenting with traumatic thoracic aortic ruptures. Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta.

PubMed

Cheheltani, Rabee; McGoverin, Cushla M; Rao, Jayashree; Vorp, David A; Kiani, Mohammad F; Pleshko, Nancy

2014-06-21

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues.

Fourier Transform Infrared Spectroscopy to Quantify Collagen and Elastin in an In Vitro Model of Extracellular Matrix Degradation in Aorta

PubMed Central

Cheheltani, Rabee; McGoverin, Cushla M.; Rao, Jayashree; Vorp, David A.; Kiani, Mohammad F.; Pleshko, N.

2014-01-01

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues. PMID:24761431

A Structural Finite Element Model for Lamellar Unit of Aortic Media Indicates Heterogeneous Stress Field After Collagen Recruitment

PubMed Central

Thunes, James R.; Pal, Siladitya; Fortunato, Ronald N.; Phillippi, Julie A.; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2016-01-01

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue. Motivated by this need, we developed a finite element based three-dimensional structural model of the lamellar units of the ATA media that directly incorporates the collagen fiber microarchitecture. The fiber architecture was computer generated utilizing network features, namely fiber orientation distribution, intersection density and areal concentration, obtained from image analysis of multiphoton microscopy images taken from human aneurysmal ascending thoracic aortic media specimens with bicuspid aortic valve (BAV) phenotype. Our model reproduces the typical J-shaped constitutive response of the aortic wall tissue. We found that the stress state in the non-fibrous matrix was homogeneous until the collagen fibers were recruited, but became highly heterogeneous after that event. The degree of heterogeneity was dependent upon local network architecture with high stresses observed near disrupted fibers. The magnitude of non-fibrous matrix stress at higher stretch levels was negatively correlated with local fiber density. The localized stress concentrations, elucidated by this model, may be a factor in the degenerative changes in aneurysmal ATA tissue. PMID:27113538

Aortic Root Biomechanics After Sleeve and David Sparing Techniques: A Finite Element Analysis.

PubMed

Tasca, Giordano; Selmi, Matteo; Votta, Emiliano; Redaelli, Paola; Sturla, Francesco; Redaelli, Alberto; Gamba, Amando

2017-05-01

Aortic root aneurysm can be treated with valve-sparing procedures. The David and Yacoub techniques have shown excellent long-term results but are technically demanding. Recently, a new and simpler procedure, the Sleeve technique, was proposed with encouraging results. We aimed to quantify the biomechanics of the initially aneurysmal aortic root (AR) after the Sleeve procedure to assess whether it induces abnormal stresses, potentially undermining its durability. Two finite element (FE) models of the physiologic and aneurysmal AR were built, accounting for the anatomical asymmetry and the nonlinear and anisotropic mechanical properties of human AR tissues. On the aneurysmal model, the Sleeve and David techniques were simulated based on the corresponding published technical features. Aortic root biomechanics throughout 2 consecutive cardiac cycles were computed in each simulated configuration. Both sparing techniques restored physiologic-like kinematics of aortic valve (AV) leaflets but induced different leaflets stresses. The time course averaged over the leaflets' bellies was 35% higher in the David model than in the Sleeve model. Commissural stresses, which were equal to 153 and 318 kPa in the physiologic and aneurysmal models, respectively, became 369 and 208 kPa in the David and Sleeve models, respectively. No intrinsic structural problems were detected in the Sleeve model that might jeopardize the durability of the procedure. If corroborated by long-term clinical outcomes, the results obtained suggest that using this new technique could successfully simplify the surgical repair of AR aneurysms and reduce intraoperative complications. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

Artificial aortic valve dysfunction due to pannus and thrombus – different methods of cardiac surgical management

PubMed Central

Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

2015-01-01

Introduction Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. Case study 1 The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs’ surface was found. A biological aortic prosthesis was reimplanted without complications. Case study 2 The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored. Conclusions Precise and modern diagnostic methods facilitated selection of the treatment method. However, the intraoperative view also seems to be crucial in individualizing the surgical approach. PMID:26702274

Artificial aortic valve dysfunction due to pannus and thrombus - different methods of cardiac surgical management.

PubMed

Ostrowski, Stanisław; Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

2015-09-01

Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs' surface was found. A biological aortic prosthesis was reimplanted without complications. The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored. Precise and modern diagnostic methods facilitated selection of the treatment method. However, the intraoperative view also seems to be crucial in individualizing the surgical approach.

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

2013-07-01

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r2 in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r2) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics.

Effects of Different Exercise Modes on Arterial Stiffness and Nitric Oxide Synthesis.

PubMed

Hasegawa, Natsuki; Fujie, Shumpei; Horii, Naoki; Miyamoto-Mikami, Eri; Tsuji, Katsunori; Uchida, Masataka; Hamaoka, Takafumi; Tabata, Izumi; Iemitsu, Motoyuki

2018-06-01

Aerobic training (AT) and high-intensity intermittent training (HIIT) reduce arterial stiffness, whereas resistance training (RT) induces deterioration of or no change in arterial stiffness. However, the molecular mechanism of these effects of different exercise modes remains unclear. This study aimed to clarify the difference of different exercise effects on endothelial nitric oxide synthase (eNOS) signaling pathway and arterial stiffness in rats and humans. In the animal study, forty 10-wk-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (CON), AT (treadmill running, 60 min at 30 m·min, 5 d·wk for 8 wk), RT (ladder climbing, 8-10 sets per day, 3 d·wk for 8 wk), and HIIT (14 repeats of 20-s swimming session with 10-s pause between sessions, 4 d·wk for 6 wk from 12-wk-old) groups (n = 10 in each group). In the human study, we confirmed the effects of 6-wk HIIT and 8-wk AT interventions on central arterial stiffness and plasma nitrite/nitrate level in untrained healthy young men in randomized controlled trial (HIIT, AT, and CON; n = 7 in each group). In the animal study, the effect on aortic pulse wave velocity (PWV), as an index of central arterial stiffness, after HIIT was the same as the decrease in aortic PWV and increase in arterial eNOS/Akt phosphorylation after AT, which was not changed by RT. A negative correlation between aortic PWV and eNOS phosphorylation was observed (r = -0.38, P < 0.05). In the human study, HIIT- and AT-induced changes in carotid-femoral PWV (HIIT -115.3 ± 63.4 and AT -157.7 ± 45.7 vs CON 71.3 ± 61.1 m·s, each P < 0.05) decreased, and plasma nitrite/nitrate level increased compared with those in CON. HIIT may reduce central arterial stiffness via the increase in aortic nitric oxide bioavailability despite it being done in a short time and short term and has the same effects as AT.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

PubMed

Beckmann, A; Hamm, C; Figulla, H R; Cremer, J; Kuck, K H; Lange, R; Zahn, R; Sack, S; Schuler, G C; Walther, T; Beyersdorf, F; Böhm, M; Heusch, G; Funkat, A K; Meinertz, T; Neumann, T; Papoutsis, K; Schneider, S; Welz, A; Mohr, F W

2012-07-01

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hyperphosphatemia induces cellular senescence in human aorta smooth muscle cells through integrin linked kinase (ILK) up-regulation.

PubMed

Troyano, Nuria; Nogal, María Del; Mora, Inés; Diaz-Naves, Manuel; Lopez-Carrillo, Natalia; Sosa, Patricia; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruiz-Torres, María P

2015-12-01

Aging is conditioned by genetic and environmental factors. Hyperphosphatemia is related to some pathologies, affecting to vascular cells behavior. This work analyze whether high concentration of extracellular phosphate induces vascular smooth muscle cells senescence, exploring the intracellular mechanisms and highlighting the in vivo relevance of this phenomenon. Human aortic smooth muscle cells treated with β-Glycerophosphate (BGP, 10mM) suffered cellular senescence by increasing p53, p21 and p16 expression and the senescence associated β-galactosidase activity. In parallel, BGP induced ILK overexpression, dependent on the IGF-1 receptor activation, and oxidative stress. Down-regulating ILK expression prevented BGP-induced senescence and oxidative stress. Aortic rings from young rats treated with 10mM BGP for 48h, showed increased p53, p16 and ILK expression and SA-β-gal activity. Seven/eight nephrectomized rats feeding a hyperphosphatemic diet and fifteenth- month old mice showed hyperphosphatemia and aortic ILK, p53 and p16 expression. In conclusion, we demonstrated that high extracellular concentration of phosphate induced senescence in cultured smooth muscle through the activation of IGF-1 receptor and ILK overexpression and provided solid evidences for the in vivo relevance of these results since aged animals showed high levels of serum phosphate linked to increased expression of ILK and senescence genes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Web-based nomogram predicting para-aortic nodal metastasis in incompletely staged patients with endometrial cancer: a Korean Multicenter Study.

PubMed

Kang, Sokbom; Lee, Jong-Min; Lee, Jae-Kwan; Kim, Jae-Weon; Cho, Chi-Heum; Kim, Seok-Mo; Park, Sang-Yoon; Park, Chan-Yong; Kim, Ki-Tae

2014-03-01

The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

Manual, semiautomated, and fully automated measurement of the aortic annulus for planning of transcatheter aortic valve replacement (TAVR/TAVI): analysis of interchangeability.

PubMed

Lou, Junyang; Obuchowski, Nancy A; Krishnaswamy, Amar; Popovic, Zoran; Flamm, Scott D; Kapadia, Samir R; Svensson, Lars G; Bolen, Michael A; Desai, Milind Y; Halliburton, Sandra S; Tuzcu, E Murat; Schoenhagen, Paul

2015-01-01

Preprocedural 3-dimensional CT imaging of the aortic annular plane plays a critical role for transcatheter aortic valve replacement (TAVR) planning; however, manual reconstructions are complex. Automated analysis software may improve reproducibility and agreement between readers but is incompletely validated. In 110 TAVR patients (mean age, 81 years; 37% female) undergoing preprocedural multidetector CT, automated reconstruction of the aortic annular plane and planimetry of the annulus was performed with a prototype of now commercially available software (syngo.CT Cardiac Function-Valve Pilot; Siemens Healthcare, Erlangen, Germany). Fully automated, semiautomated, and manual annulus measurements were compared. Intrareader and inter-reader agreement, intermodality agreement, and interchangeability were analyzed. Finally, the impact of these measurements on recommended valve size was evaluated. Semiautomated analysis required major correction in 5 patients (4.5%). In the remaining 95.5%, only minor correction was performed. Mean manual annulus area was significantly smaller than fully automated results (P < .001 for both readers) but similar to semiautomated measurements (5.0 vs 5.4 vs 4.9 cm(2), respectively). The frequency of concordant recommendations for valve size increased if manual analysis was replaced with the semiautomated method (60% agreement was improved to 82.4%; 95% confidence interval for the difference [69.1%-83.4%]). Semiautomated aortic annulus analysis, with minor correction by the user, provides reliable results in the context of TAVR annulus evaluation. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome

PubMed Central

2014-01-01

Background Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined. Methods Ten consecutive BAV patients [8 men, age range 24–42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients. Results We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype. Conclusions The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing. PMID:24564502

Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?

PubMed Central

Gao, Yuan Z.; Saphirstein, Robert J.; Yamin, Rina; Suki, Bela

2014-01-01

Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small-molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of NG-nitro-l-arginine methyl ester (l-NAME) to remove interference of endothelial nitric oxide, increases stiffness by 90–200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which 1) VSMCs are a surprisingly large component of aortic stiffness at physiological lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors. PMID:25128168

Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding.

PubMed

Maaninka, Katariina; Nguyen, Su Duy; Mäyränpää, Mikko I; Plihtari, Riia; Rajamäki, Kristiina; Lindsberg, Perttu J; Kovanen, Petri T; Öörni, Katariina

2018-04-13

Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. Mature human MCs were differentiated from human peripheral blood-derived CD34 + progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium. LDL was incubated in the MC-conditioned medium or with individual MC proteases, and the binding of native and modified LDL to isolated human aortic proteoglycans or to human atherosclerotic plaques ex vivo was determined. MC proteases in atherosclerotic human coronary artery lesions were detected by immunofluorescence and qPCR. Activated human MCs released the neutral proteases tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B. Of these, cathepsin G degraded most efficiently apoB-100, induced LDL fusion, and enhanced binding of LDL to isolated human aortic proteoglycans and human atherosclerotic lesions ex vivo. Double immunofluoresence staining of human atherosclerotic coronary arteries for tryptase and cathepsin G indicated that lesional MCs contain cathepsin G. In the lesions, expression of cathepsin G correlated with the expression of tryptase and chymase, but not with that of neutrophil proteinase 3. The present study suggests that cathepsin G in human atherosclerotic lesions is largely derived from MCs and that activated MCs may contribute to atherogenesis by enhancing LDL retention. Copyright © 2018 Elsevier B.V. All rights reserved.

First uses of HAART 300 rings for aortic valve repair in Poland - 4 case studies.

PubMed

Juściński, Jacek H; Koprowski, Andrzej; Kołaczkowska, Magdalena; Kowalik, Maciej M; Rogowski, Jan A; Rankin, James S

2018-03-01

Aortic valve reconstructions using geometric annuloplasty rings HAART 300/200 open new era in aortic valve surgery. The HAART technology resizes, reshapes, stabilizes and simplifies aortic valve repair. The HAART aortic repair rings are designed to be implanted directly into aortic annulus (under aortic valve leaflets). We present first in Poland 4 cases of aortic valve reconstructions using geometric annuloplasty rings HAART 300. Two patients had type IA aortic insufficiency (due to El-Khoury classification) - they were treated by HAART 300 ring insertion and ascending aorta prosthesis implantation. Third patient, Marfan with type IB aortic insufficiency was repaired by HAART 300 ring implantation followed by remodeling (Yacoub) procedure. Fourth patient with type II aortic insufficiency (due to RCC prolapse) was repaired by HAART 300 implantation and cusp plication. All patients shows good results on 6 months postoperative 3D TTE examinations. Presented technique is reproducible and simplify aortic valve reconstructions.

Characterization of Chronic Aortic and Mitral Regurgitation Undergoing Valve Surgery Using Cardiovascular Magnetic Resonance.

PubMed

Polte, Christian L; Gao, Sinsia A; Johnsson, Åse A; Lagerstrand, Kerstin M; Bech-Hanssen, Odd

2017-06-15

Grading of chronic aortic regurgitation (AR) and mitral regurgitation (MR) by cardiovascular magnetic resonance (CMR) is currently based on thresholds, which are neither modality nor quantification method specific. Accordingly, this study sought to identify CMR-specific and quantification method-specific thresholds for regurgitant volumes (RVols), RVol indexes, and regurgitant fractions (RFs), which denote severe chronic AR or MR with an indication for surgery. The study comprised patients with moderate and severe chronic AR (n = 38) and MR (n = 40). Echocardiography and CMR was performed at baseline and in all operated AR/MR patients (n = 23/25) 10 ± 1 months after surgery. CMR quantification of AR: direct (aortic flow) and indirect method (left ventricular stroke volume [LVSV] - pulmonary stroke volume [PuSV]); MR: 2 indirect methods (LVSV - aortic forward flow [AoFF]; mitral inflow [MiIF] - AoFF). All operated patients had severe regurgitation and benefited from surgery, indicated by a significant postsurgical reduction in end-diastolic volume index and improvement or relief of symptoms. The discriminatory ability between moderate and severe AR was strong for RVol >40 ml, RVol index >20 ml/m 2 , and RF >30% (direct method) and RVol >62 ml, RVol index >31 ml/m 2 , and RF >36% (LVSV-PuSV) with a negative likelihood ratio ≤ 0.2. In MR, the discriminatory ability was very strong for RVol >64 ml, RVol index >32 ml/m 2 , and RF >41% (LVSV-AoFF) and RVol >40 ml, RVol index >20 ml/m 2 , and RF >30% (MiIF-AoFF) with a negative likelihood ratio < 0.1. In conclusion, CMR grading of chronic AR and MR should be based on modality-specific and quantification method-specific thresholds, as they differ largely from recognized guideline criteria, to assure appropriate clinical decision-making and timing of surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders: Relationships With Age, Aortic Size, Rate of Dilation, and Surgical Root Replacement.

PubMed

Prakash, Ashwin; Adlakha, Himanshu; Rabideau, Nicole; Hass, Cara J; Morris, Shaine A; Geva, Tal; Gauvreau, Kimberlee; Singh, Michael N; Lacro, Ronald V

2015-08-18

Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs. Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and β-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter z score per year. In 83 CTD patients (median age, 24 years; range, 1-55; 17% <18 years of age; 60% male), ascending aorta distensibility was reduced in comparison with published normative values: median z score, -1.93 (range, -8.7 to 1.3; P<0.0001 versus normals). Over a median follow-up period of 2.7 years, there were no aortic dissections or deaths, but 16 of 83 (19%) patients underwent surgical aortic root replacement. In multivariable analysis, lower aortic root strain (P=0.05) and higher vertebral tortuosity index (P=0.01) were independently associated with aortic root replacement. Lower ascending aorta strain (P=0.02) was associated with a higher rate of aortic root dilation. Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs. © 2015 American Heart Association, Inc.

Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure, mechanical property and biocompatibility study.

PubMed

Qiao, Wei-Hua; Liu, Peng; Hu, Dan; Al Shirbini, Mahmoud; Zhou, Xian-Ming; Dong, Nian-Guo

2018-02-01

Antigenicity of xenogeneic tissues is the major obstacle to increased use of these materials in clinical medicine. Residual xenoantigens in decellularized tissue elicit the immune response after implantation, causing graft failure. With this in mind, the potential use is proposed of three protein solubilization-based protocols for porcine aortic valve leaflets decellularization. It was demonstrated that hydrophile solubilization alone achieved incomplete decellularization; lipophile solubilization alone (LSA) completely removed all cells and two most critical xenoantigens - galactose-α(1,3)-galactose (α-Gal) and major histocompatibility complex I (MHC I) - but caused severe alterations of the structure and mechanical properties; sequential hydrophile and lipophile solubilization (SHLS) resulted in a complete removal of cells, α-Gal and MHC I, and good preservation of the structure and mechanical properties. In contrast, a previously reported method using Triton X-100, sodium deoxycholate and IGEPAL CA-630 resulted in a complete removal of all cells and MHC I, but with remaining α-Gal epitope. LSA- and SHLS-treated leaflets showed significantly reduced leucocyte activation (polymorphonuclear elastase) upon interaction with human blood in vitro. When implanted subdermally in rats for 6 weeks, LSA- or SHLS-treated leaflets were presented with more biocompatible implants and all four decellularized leaflets were highly resistant to calcification. These findings illustrate that the SHLS protocol could be considered as a promising decellularization method for the decellularization of xenogeneic tissues in tissue engineering and regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Biosynthesis of fibronectin by rabbit aorta.

PubMed

Takasaki, I; Chobanian, A V; Brecher, P

1991-09-15

The in vitro interactions between vascular cells and fibronectin have been shown to influence phenotypic expression of both cultured endothelial and smooth muscle cells. To more effectively assess the potential functional role of fibronectin in vivo in modulating vascular phenotypes, we have established methodology for studying fibronectin biosynthesis in the rabbit aorta using aortic rings that are morphologically and functionally intact and metabolically active. Aortic rings were incubated with 35S-labeled methionine in a supplemented physiological salt solution. The tissue was fractionated, and quantitative immunoprecipitation was performed using a polyclonal antibody directed against human plasma fibronectin. Newly synthesized fibronectin was most abundant in the fraction solubilized using 4% sodium dodecyl sulfate and in the incubation medium. In all fractions studied, fibronectin was present predominantly as a dimer with no detectable aggregates of fibronectin. Pulse-chase experiments showed that a substantial amount of newly synthesized fibronectin was found in the 4% sodium dodecyl sulfate extract after only 1 h, suggesting that fibronectin was rapidly incorporated into the extracellular matrix. The more soluble forms of newly synthesized fibronectin appeared to be the precursors for secreted fibronectin, and no precursor-product relationship between soluble and insoluble fibronectin was found. Dissection of aortic rings following incubation with labeled methionine showed that newly synthesized fibronectin was uniformally distributed in both intima-media and media-adventitia segments. Endothelial cell denudation caused only a 20% decrease of fibronectin biosynthesis concomitant with similar changes in total protein biosynthesis, consistent with the medial smooth muscle cell as the major source of newly synthesized fibronectin. Biosynthesis of fibronectin was increased following a 24-h preincubation of the aortic rings, and concomitant increases in steady state mRNA for fibronectin were found. These in vitro studies documented the utility of aortic rings for the general purpose of studying protein synthesis in vascular cells and provide new information on the characteristics of fibronectin biosynthesis by aortic tissue.

How Heart Valves Evolve to Adapt to an Extreme-Pressure System: Morphologic and Biomechanical Properties of Giraffe Heart Valves.

PubMed

Amstrup Funder, Jonas; Christian Danielsen, Carl; Baandrup, Ulrik; Martin Bibby, Bo; Carl Andelius, Ted; Toft Brøndum, Emil; Wang, Tobias; Michael Hasenkam, J

2017-01-01

Heart valves which exist naturally in an extreme-pressure system must have evolved in a way to resist the stresses of high pressure. Giraffes are interesting as they naturally have a blood pressure twice that of humans. Thus, knowledge regarding giraffe heart valves may aid in developing techniques to design improved pressure-resistant biological heart valves. Heart valves from 12 giraffes and 10 calves were explanted and subjected to either biomechanical or morphological examinations. Strips from the heart valves were subjected to cyclic loading tests, followed by failure tests. Thickness measurements and analyses of elastin and collagen content were also made. Valve specimens were stained with hematoxylin and eosin, elastic van Gieson stain, Masson's trichrome and Fraser-Lendrum stain, as well as immunohistochemical reactions for morphological examinations. The aortic valve was shown to be 70% (95% CI 42-103%) stronger in the giraffe than in its bovine counterpart (p <0.001). No significant difference was found between mitral or pulmonary valves. After normalization for collagen, no significant differences were found in strength between species. The giraffe aortic valve was found to be significantly stiffer than the bovine aortic valve (p <0.001), with no significant difference between mitral and pulmonary valves. On a dry weight basis, the aortic (10.9%), pulmonary (4.3%), and mitral valves (9.6%) of giraffes contained significantly more collagen than those of calves. The elastin contents of the pulmonary valves (2.5%) and aortic valves (1.5%) were also higher in giraffes. The greater strength of the giraffe aortic valve is most likely due to a compact collagen construction. Both, collagen and elastin contents were higher in giraffes than in calves, which would make giraffe valves more resistant to the high-pressure forces. However, collagen also stiffens and thickens the valves. The mitral leaflets showed similar (but mostly insignificant) trends in strength, stiffness, and collagen content.

[Endovascular and surgical treatment of a patient with traumatic rupture of the aorta and hepatic artery].

PubMed

Chernaya, N R; Muslimov, R Sh; Selina, I E; Kokov, L S; Vladimirova, E S; Navruzbekov, M S; Gulyaev, V A

2016-01-01

Traumatic rupture of the aorta is the second most common cause of death in closed chest injury. The latest findings of autopsy showed that 80% of lethal outcomes in aortic injury occur in the prehospital period. Taking into consideration the incidence and high rate of death prior to the diagnosis stage, aortic rupture in closed thoracic injury is an important problem. Due to the characteristic mechanism of the development (during sharp deceleration of the body) this type of traumatic lesion of the aorta became known as "deceleration syndrome". The most vulnerable to tension aortic portion is its neck where the mobile part of the thoracic aorta is connected to the fixed arch in the place of the arterial ligament attachment. Open surgical intervention in patients with severe closed chest injury (often concomitant injury) is associated with high mortality and complications. Currently endovascular prosthetic repair of the aorta is a method of choice at the primary stage of treatment of patients with aortic injury. In this article we present a rare case report of concomitant lesion of large vessels (the descending aortic portion and proper hepatic artery) in a patient with severe concomitant injury, as well as peculiarities of diagnosis and combined treatment (endovascular prosthetic repair of the aorta and hepatic artery with an aotovein).

Is Conventional Open Repair for Abdominal Aortic Aneurysm Feasible in Nonagenarians?

PubMed

Uehara, Kyokun; Matsuda, Hitoshi; Inoue, Yosuke; Omura, Atsushi; Seike, Yoshimasa; Sasaki, Hiroaki; Kobayashi, Junjiro

2017-09-25

Background : Although endovascular repair for abdominal aortic aneurysm has been found to be beneficial in very elderly patients, some patients have contraindications to this procedure. For nonagenarians, the results of open repair remain unclear. The purpose of this study was to compare the outcomes of open vs. endovascular repair for abdominal aortic aneurysm in nonagenarian patients. Methods and Results : Fourteen patients undergoing open surgical repair and 24 undergoing endovascular repair for abdominal aortic aneurysm were evaluated. There was no significant difference in early mortality between the open and endovascular groups (0% vs. 4.1%, p=0.16). The open repair group required much longer hospital stays (26.4 vs. 10.6 days, respectively, p=0.003). Finally, 12 patients (86%) undergoing open repair vs. 21 (88%) undergoing endovascular repair returned home (p=0.49). During a mean follow-up period of 23.4±23.5 months, cumulative estimated 1- and 3-year survival rates were 90.0% and 48.0%, respectively in the open repair group and 90.6% and 54.9%, respectively in the endovascular repair group (p=0.51). Conclusion : Although endovascular repair for abdominal aortic aneurysm was superior in terms of recovery, the results of conventional open repair were acceptable even in nonagenarian patients. Open repair remains an alternative for patients with contraindications to endovascular repair.

Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation

PubMed Central

Spina, Roberto; Anthony, Chris; Muller, David WM

2015-01-01

Transcatheter aortic valve replacement with either the balloon-expandable Edwards SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the established therapeutic modality for severe aortic valve stenosis in patients who are not deemed suitable for surgical intervention due to excessively high operative risk. Native aortic valve regurgitation, defined as primary aortic incompetence not associated with aortic stenosis or failed valve replacement, on the other hand, is still considered a relative contraindication for transcatheter aortic valve therapies, because of the absence of annular or leaflet calcification required for secure anchoring of the transcatheter heart valve. In addition, severe aortic regurgitation often coexists with aortic root or ascending aorta dilatation, the treatment of which mandates operative intervention. For these reasons, transcatheter aortic valve replacement has been only sporadically used to treat pure aortic incompetence, typically on a compassionate basis and in surgically inoperable patients. More recently, however, transcatheter aortic valve replacement for native aortic valve regurgitation has been trialled with newer-generation heart valves, with encouraging results, and new ancillary devices have emerged that are designed to stabilize the annulus–root complex. In this paper we review the clinical context, technical characteristics and outcomes associated with transcatheter treatment of native aortic valve regurgitation. PMID:29588674

Durability of central aortic valve closure in patients with continuous flow left ventricular assist devices.

PubMed

McKellar, Stephen H; Deo, Salil; Daly, Richard C; Durham, Lucian A; Joyce, Lyle D; Stulak, John M; Park, Soon J

2014-01-01

A competent aortic valve is essential to providing effective left ventricular assist device support. We have adopted a practice of central aortic valve closure by placing a simple coaptation stitch at left ventricular assist device implantation in patients with significant aortic insufficiency. We conducted a follow-up study to evaluate the efficacy and durability of this procedure. The study included patients who had undergone continuous flow left ventricular assist device implantation. The patients were divided into 2 groups, those who did not require any aortic procedure because the valve was competent and those who underwent central aortic valve closure for mild or greater aortic regurgitation. The clinical endpoints were mortality, progression or recurrence of aortic insufficiency, and reoperation for aortic valve pathologic features. Aortic insufficiency was measured qualitatively from mild to severe on a scale of 0 to 5. A total of 123 patients received continuous flow left ventricular assist devices from February 2007 to August 2011. Of those, 18 (15%) underwent central aortic valve closure at left ventricular assist device implantation because of significant aortic insufficiency (1.8 ± 1.4) and 105 who did not (competent aortic valve, 0.15 ± 0.43; P < .01). At follow-up (median, 312 days; range, 0-1429 days), the mean aortic insufficiency score remained low for the patients with central aortic valve closure (0.27 ± 0.46) in contrast to those without central aortic valve closure who experienced aortic insufficiency progression (0.78 ± 0.89; P = .02). In addition, the proportion of patients with more than mild aortic insufficiency was significantly less in the central aortic valve closure group (0% vs 18%; P = .05). The patients in the central aortic valve closure group were significantly older and had a greater incidence of renal failure at baseline. The 30-day mortality was greater in the central aortic valve closure group, but the late survival was similar between the 2 groups. No reoperations were required for recurrent aortic insufficiency. The results of our study have shown that repair of aortic insufficiency with a simple central coaptation stitch is effective and durable in left ventricular assist device-supported patients, with follow-up extending into 2 years. Although aortic insufficiency progressed over time in those with minimal native valve regurgitation initially, no such progression was noted in those with central aortic valve closure. Additional investigation is needed to evaluate whether prophylactic central aortic valve closure should be performed at left ventricular assist device implantation to avoid problematic aortic regurgitation developing over time, in particular in patients undergoing left ventricular assist device implantation for life-long (destination therapy) support. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing.

PubMed

Sun, Jie; Chen, Guojun; Jing, Yuanwen; He, Xiang; Dong, Jianting; Zheng, Junmeng; Zou, Meisheng; Li, Hairui; Wang, Shifei; Sun, Yili; Liao, Wangjun; Liao, Yulin; Feng, Li; Bin, Jianping

2018-01-01

In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, P< 0.05). QRT-PCR results of five dysregulated genes were consistent with HTS data. A lncRNA-mRNA coexpression analysis showed positive correlations between the up-regulated lncRNA (ENSG00000269936) and its adjacent up-regulated mRNA (MAP2K6, R=0.940, P< 0.01), and between the down-regulated lncRNA_1421 and its down-regulated mRNAs (FBLN5, R=0.950, P< 0.01; ACTA2, R=0.96, P< 0.01; TIMP3, R=0.96, P< 0.05). The lncRNA-miRNA-mRNA network indicated that the up-regulated lncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p. The results of luciferase assay and fluorescence immuno-cytochemistry were consistent with that. And qRT-PCR results showed that lncRNA XIST and p21 were expressed at a higher level and has-miR-17-5p was expressed at a lower level in TAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, P< 0.001; R=0.967, P< 0.01; R=0.960, P< 0.01, respectively). Our study revealed a set of dysregulated lncRNAs and predicted their multiple potential functions in human TAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD. © 2018 The Author(s). Published by S. Karger AG, Basel.

3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model.

PubMed

Spühler, Jeannette H; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

2018-01-01

Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework.

Quantified degree of eccentricity of aortic valve calcification predicts risk of paravalvular regurgitation and response to balloon post-dilation after self-expandable transcatheter aortic valve replacement.

PubMed

Park, Jun-Bean; Hwang, In-Chang; Lee, Whal; Han, Jung-Kyu; Kim, Chi-Hoon; Lee, Seung-Pyo; Yang, Han-Mo; Park, Eun-Ah; Kim, Hyung-Kwan; Chiam, Paul T L; Kim, Yong-Jin; Koo, Bon-Kwon; Sohn, Dae-Won; Ahn, Hyuk; Kang, Joon-Won; Park, Seung-Jung; Kim, Hyo-Soo

2018-05-15

Limited data exist regarding the impact of aortic valve calcification (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response to balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value of AVC eccentricity in predicting the risk of PVR and response to BPD in patients undergoing TAVR. We analyzed 85 patients with severe aortic stenosis who underwent self-expandable TAVR (43 women; 77.2±7.1years). AVC was quantified as the total amount of calcification (total AVC load) and as the eccentricity of calcium (EoC) using calcium volume scoring with contrast computed tomography angiography (CTA). The EoC was defined as the maximum absolute difference in calcium volume scores between 2 adjacent sectors (bi-partition method) or between sectors based on leaflets (leaflet-based method). Total AVC load and bi-partition EoC, but not leaflet-based EoC, were significant predictors for the occurrence of ≥moderate PVR, and bi-partition EoC had a better predictive value than total AVC load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In multivariate analysis, bi-partition EoC was an independent predictor for the risk of ≥moderate PVR regardless of perimeter oversizing index. The greater bi-partition EoC was the only significant parameter to predict poor response to BPD (AUC=0.775, p=0.004). Pre-procedural assessment of AVC eccentricity using CTA as "bi-partition EoC" provides useful predictive information on the risk of significant PVR and response to BPD in patients undergoing TAVR with self-expandable valves. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection

PubMed Central

Rausch, Laura A.; Kouchoukos, Nicholas T.; Lobdell, Kevin W.; Khabbaz, Kamal; Murphy, Edward; Hagberg, Robert C.

2016-01-01

Background The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. Methods A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Results Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102–0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962–1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). Conclusions During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection. PMID:27563545

Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study

PubMed Central

Tastet, Lionel; Capoulade, Romain; Clavel, Marie-Annick; Larose, Éric; Shen, Mylène; Dahou, Abdellaziz; Arsenault, Marie; Mathieu, Patrick; Bédard, Élisabeth; Dumesnil, Jean G.; Tremblay, Alexe; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe

2017-01-01

Aims Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. Methods and results The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile–75th percentile]: +370 [126–824] vs. +157 [58–303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34–218] vs. +45 [14–82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3–199] vs. +41 [0–156] AU, P = 0.88). Conclusion This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS. PMID:26896413

3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model

PubMed Central

Spühler, Jeannette H.; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

2018-01-01

Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework. PMID:29713288

Fibrinogen concentrate as first-line therapy in aortic surgery reduces transfusion requirements in patients with platelet counts over or under 100×109/L

PubMed Central

Solomon, Cristina; Rahe-Meyer, Niels

2015-01-01

Background Administration of fibrinogen concentrate, targeting improved maximum clot firmness (MCF) of the thromboelastometric fibrin-based clot quality test (FIBTEM) is effective as first-line haemostatic therapy in aortic surgery. We performed a post-hoc analysis of data from a randomised, placebo-controlled trial of fibrinogen concentrate, to investigate whether fibrinogen concentrate reduced transfusion requirements for patients with platelet counts over or under 100×109/L. Material and methods Aortic surgery patients with coagulopathic bleeding after cardiopulmonary bypass were randomised to receive either fibrinogen concentrate (n=29) or placebo (n=32). Platelet count was measured upon removal of the aortic clamp, and coagulation and haematology parameters were measured peri-operatively. Transfusion of allogeneic blood components was recorded and compared between groups. Results After cardiopulmonary bypass, haemostatic and coagulation parameters worsened in all groups; plasma fibrinogen level (determined by the Clauss method) decreased by 43–58%, platelet count by 53–64%, FIBTEM maximum clot firmness (MCF) by 38–49%, FIBTEM maximum clot elasticity (MCE) by 43–54%, extrinsically activated test (EXTEM) MCF by 11–22%, EXTEM MCE by 25–41% and the platelet component of the clot by 23–39%. Treatment with fibrinogen concentrate (mean dose 7–9 g in the 4 groups) significantly reduced post-operative allogeneic blood component transfusion requirements when compared to placebo both for patients with a platelet count ≥100×109/L and for patients with a platelet count <100×109/L. Discussion FIBTEM-guided administration of fibrinogen concentrate reduced transfusion requirements when used as a first-line haemostatic therapy during aortic surgery in patients with platelet counts over or under 100×109/L. PMID:25369608

In situ label-free quantification of human pluripotent stem cells with electrochemical potential.

PubMed

Yea, Cheol-Heon; Jeong, Ho-Chang; Moon, Sung-Hwan; Lee, Mi-Ok; Kim, Kyeong-Jun; Choi, Jeong-Woo; Cha, Hyuk-Jin

2016-01-01

Conventional methods for quantification of undifferentiated pluripotent stem cells such as fluorescence-activated cell sorting and real-time PCR analysis have technical limitations in terms of their sensitivity and recyclability. Herein, we designed a real-time in situ label-free monitoring system on the basis of a specific electrochemical signature of human pluripotent stem cells in vitro. The intensity of the signal of hPSCs highly corresponded to the cell number and remained consistent in a mixed population with differentiated cells. The electrical charge used for monitoring did not markedly affect the proliferation rate or molecular characteristics of differentiated human aortic smooth muscle cells. After YM155 treatment to ablate undifferentiated hPSCs, their specific signal was significantly reduced. This suggests that detection of the specific electrochemical signature of hPSCs would be a valid approach to monitor potential contamination of undifferentiated hPSCs, which can assess the risk of teratoma formation efficiently and economically. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement.

PubMed

Polimenakos, Anastasios C; Sathanandam, Shyam; Elzein, Chawki; Barth, Mary J; Higgins, Robert S D; Ilbawi, Michel N

2010-04-01

Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. There were no early, intermediate, or late deaths. Z-values of left ventricular end-diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

PubMed Central

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Micro-computed Tomography Provides High Accuracy Congenital Heart Disease Diagnosis in Neonatal and Fetal Mice

PubMed Central

Kim, Andrew J.; Francis, Richard; Liu, Xiaoqin; Devine, William A.; Ramirez, Ricardo; Anderton, Shane J.; Wong, Li Yin; Faruque, Fahim; Gabriel, George C.; Leatherbury, Linda; Tobita, Kimimasa; Lo, Cecilia W.

2013-01-01

Background Mice are well suited for modeling human congenital heart defects (CHD), given their four-chamber cardiac anatomy. However, mice with CHD invariably die prenatally/neonatally, causing CHD phenotypes to be missed. Therefore, we investigated the efficacy of noninvasive micro-computed tomography (micro-CT) to screen for CHD in stillborn/fetal mice. These studies were carried out using chemically mutagenized mice expected to be enriched for birth defects including CHD. Methods and Results Stillborn/fetal mice obtained from the breeding of N-ethyl-N-nitrosourea (ENU) mutagenized mice were formalin-fixed and stained with iodine, then micro-CT scanned. Those diagnosed with CHD and some CHD-negative pups were necropsied. A subset of these were further analyzed by histopathology to confirm the CHD/no-CHD diagnosis. Micro-CT scanning of 2105 fetal/newborn mice revealed an abundance of ventricular septal defects (VSD) (n=307). Overall, we observed an accuracy of 89.8% for VSD diagnosis. Outflow tract anomalies identified by micro-CT included double outlet right ventricle (n=36), transposition of the great arteries (n=14), and persistent truncus arteriosus (n=3). These were diagnosed with a 97.4% accuracy. Aortic arch anomalies also were readily detected with an overall 99.6% accuracy. This included right aortic arch (n=28) and coarctation/interrupted aortic arch (n=12). Also detected by micro-CT were atrioventricular septal defects (n=22), tricuspid hypoplasia/atresia (n=13), and coronary artery fistulas (n=16). They yielded accuracies of 98.9%, 100%, and 97.8% respectively. Conclusions Contrast enhanced micro-CT imaging in neonatal/fetal mice can reliably detect a wide spectrum of CHD. We conclude micro-CT imaging can be used for routine rapid assessments of structural heart defects in fetal/newborn mice. PMID:23759365

Fully automated contour detection of the ascending aorta in cardiac 2D phase-contrast MRI.

PubMed

Codari, Marina; Scarabello, Marco; Secchi, Francesco; Sforza, Chiarella; Baselli, Giuseppe; Sardanelli, Francesco

2018-04-01

In this study we proposed a fully automated method for localizing and segmenting the ascending aortic lumen with phase-contrast magnetic resonance imaging (PC-MRI). Twenty-five phase-contrast series were randomly selected out of a large population dataset of patients whose cardiac MRI examination, performed from September 2008 to October 2013, was unremarkable. The local Ethical Committee approved this retrospective study. The ascending aorta was automatically identified on each phase of the cardiac cycle using a priori knowledge of aortic geometry. The frame that maximized the area, eccentricity, and solidity parameters was chosen for unsupervised initialization. Aortic segmentation was performed on each frame using active contouring without edges techniques. The entire algorithm was developed using Matlab R2016b. To validate the proposed method, the manual segmentation performed by a highly experienced operator was used. Dice similarity coefficient, Bland-Altman analysis, and Pearson's correlation coefficient were used as performance metrics. Comparing automated and manual segmentation of the aortic lumen on 714 images, Bland-Altman analysis showed a bias of -6.68mm 2 , a coefficient of repeatability of 91.22mm 2 , a mean area measurement of 581.40mm 2 , and a reproducibility of 85%. Automated and manual segmentation were highly correlated (R=0.98). The Dice similarity coefficient versus the manual reference standard was 94.6±2.1% (mean±standard deviation). A fully automated and robust method for identification and segmentation of ascending aorta on PC-MRI was developed. Its application on patients with a variety of pathologic conditions is advisable. Copyright © 2017 Elsevier Inc. All rights reserved.

A new method for precise determination of endograft position and apposition in the aortic neck after endovascular aortic aneurysm repair.

PubMed

VAN Noort, Kim; Schuurmann, Richte C; Slump, Cornelis H; Vos, Jan A; Devries, Jean P

2016-10-01

Follow-up imaging after endovascular aortic aneurysm repair (EVAR) focuses on detection of gross abnormalities: endoleaks and significant (>10 mm) migration. Precise determination of endograft position and wall apposition may predict late complications. We present a new measurement method to determine precise position and apposition of endografts in the aortic neck. Four patients were selected from our EVAR database. These patients had late (>1 year) type IA endoleak or >1 cm endograft migration. Twenty patients with uneventful follow-up were measured as controls. The new software adds six parameters to define endograft position and neck apposition: fabric distance to renal arteries, tilt, endograft expansion (% of the maximum original diameter), neck surface, apposition surface, and shortest apposition length. These parameters were determined on preoperative and all available postoperative CT-scans, to detect subtle changes during follow-up. All patients with endoleak or migration had increases in fabric distance, tilt, or endograft expansion or decrease of apposition surface. Changes occurred at least one CT scan before the endoleak or migration was noted in the CT reports. The patient without complications showed no changes in position or apposition during follow-up. The new measurement method detected subtle changes in endograft position and apposition during CT follow-up, not recognized initially. It can potentially determine endograft movements and decrease of apposition surface before they lead to complications like type IA endoleaks or uncorrectable migration. A larger follow-up study comparing complicated and non-complicated EVAR patients is needed to corroborate these results.

Landmark lecture: Perloff lecture: Tribute to Professor Joseph Kayle Perloff and lessons learned from him: aortopathy in adults with CHD.

PubMed

Niwa, Koichiro

2017-12-01

Marfan syndrome, bicuspid aortic valve, and/or coarctation of the aorta are associated with medial abnormalities of the ascending aortic or para-coarctation aorta. Medial abnormalities in the ascending aorta are prevalent in other type of patients with a variety of CHDs such as single ventricle, persistent truncus arteriosus, transposition of the great arteries, hypoplastic left heart syndrome, and tetralogy of Fallot, encompassing a wide age range and may predispose to dilatation, aneurysm, and rapture necessitating aortic valve and root surgery. These CHDs exhibit ongoing dilatation of the aortic root and reduced aortic elasticity and increased aortic stiffness that may relate to intrinsic properties of the aortic root. These aortic dilatation and increased stiffness can induce aortic aneurysm, rapture of the aorta, and aortic regurgitation, but also provoke left ventricular hypertrophy, reduced coronary artery flow, and left ventricular failure. Therefore, a new clinical entity can be used to call this association of aortic pathophysiological abnormality, aortic dilation, and aorto-left ventricular interaction - "aortopathy".

Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta.

PubMed

Persson, A; Brismar, T B; Lundström, C; Dahlström, N; Othberg, F; Smedby, O

2006-03-01

To compare three methods for standardizing volume rendering technique (VRT) protocols by studying aortic diameter measurements in magnetic resonance angiography (MRA) datasets. Datasets from 20 patients previously examined with gadolinium-enhanced MRA and with digital subtraction angiography (DSA) for abdominal aortic aneurysm were retrospectively evaluated by three independent readers. The MRA datasets were viewed using VRT with three different standardized transfer functions: the percentile method (Pc-VRT), the maximum-likelihood method (ML-VRT), and the partial range histogram method (PRH-VRT). The aortic diameters obtained with these three methods were compared with freely chosen VRT parameters (F-VRT) and with maximum intensity projection (MIP) concerning inter-reader variability and agreement with the reference method DSA. F-VRT parameters and PRH-VRT gave significantly higher diameter values than DSA, whereas Pc-VRT gave significantly lower values than DSA. The highest interobserver variability was found for F-VRT parameters and MIP, and the lowest for Pc-VRT and PRH-VRT. All standardized VRT methods were significantly superior to both MIP and F-VRT in this respect. The agreement with DSA was best for PRH-VRT, which was the only method with a mean error below 1 mm and which also had the narrowest limits of agreement (95% of cases between 2.1 mm below and 3.1 mm above DSA). All the standardized VRT methods compare favorably with MIP and VRT with freely selected parameters as regards interobserver variability. The partial range histogram method, although systematically overestimating vessel diameters, gives results closest to those of DSA.

Review of numerical methods for simulation of the aortic root: Present and future directions

NASA Astrophysics Data System (ADS)

Mohammadi, Hossein; Cartier, Raymond; Mongrain, Rosaire

2016-05-01

Heart valvular disease is still one of the main causes of mortality and morbidity in develop countries. Numerical modeling has gained considerable attention in studying hemodynamic conditions associated with valve abnormalities. Simulating the large displacement of the valve in the course of the cardiac cycle needs a well-suited numerical method to capture the natural biomechanical phenomena which happens in the valve. The paper aims to review the principal progress of the numerical approaches for studying the hemodynamic of the aortic valve. In addition, the future directions of the current approaches as well as their potential clinical applications are discussed.

Normal Pregnancy Is Associated with Changes in Central Hemodynamics and Enhanced Recruitable, but Not Resting, Endothelial Function

PubMed Central

Zócalo, Yanina; Farro, Ignacio; Farro, Federico; Scasso, Santiago; Bia, Daniel

2015-01-01

Introduction. Flow-mediated dilation (FMD), low flow-mediated constriction (L-FMC), and reactive hyperemia-related changes in carotid-to-radial pulse wave velocity (ΔPWVcr%) could offer complementary information about both “recruitability” and “resting” endothelial function (EF). Carotid-to-femoral pulse wave velocity (PWVcf) and pulse wave analysis-derived parameters (i.e., AIx@75) are the gold standard methods for noninvasive evaluation of aortic stiffness and central hemodynamics. If healthy pregnancy is associated with both changes in resting and recruitable EF, as well as in several arterial parameters, it remains unknown and/or controversial. Objectives. To simultaneously and noninvasively assess in healthy pregnant (HP) and nonpregnant (NP) women central parameters in conjunction with “basal and recruitable” EF, employing new complementary approaches. Methods. HP (n = 11, 34.2 ± 3.3 weeks of gestation) and age- and cardiovascular risk factors-matched NP (n = 22) were included. Aortic blood pressure (BP), AIx@75, PWVcf, common carotid stiffness, and intima-media thickness, as well as FMD, L-FMC, and ΔPWVcr %, were measured. Results. Aortic BP, stiffness, and AIx@75 were reduced in HP. ΔPWVcr% and FMD were enhanced in HP in comparison to NP. No differences were found in L-FMC between groups. Conclusion. HP is associated with reduced aortic stiffness, central BP, wave reflections, and enhanced recruitable, but not resting, EF. PMID:26421317

Determining arterial wave transit time from a single aortic pressure pulse in rats: vascular impulse response analysis.

PubMed

Chang, Ru-Wen; Chang, Chun-Yi; Lai, Liang-Chuan; Wu, Ming-Shiou; Young, Tai-Horng; Chen, Yih-Sharng; Wang, Chih-Hsien; Chang, Kuo-Chu

2017-01-19

Arterial wave transit time (τ w ) in the lower body circulation is an effective biomarker of cardiovascular risk that substantially affects systolic workload imposed on the heart. This study evaluated a method for determining τ w from the vascular impulse response on the basis of the measured aortic pressure and an assumed triangular flow (Q tri ). The base of the unknown Q tri was constructed with a duration set equal to ejection time. The timing of the peak triangle was derived using a fourth-order derivative of the pressure waveform. Values of τ w s obtained using Q tri were compared with those obtained from the measure aortic flow wave (Q m ). Healthy rats (n = 27), rats with chronic kidney disease (CKD; n = 22), and rats with type 1 (n = 22) or type 2 (n = 11) diabetes were analyzed. The cardiovascular conditions in the CKD rats and both diabetic groups were characterized by a decrease in τ w s. The following significant relation was observed (P < 0.0001): τ w triQ  = -1.5709 + 1.0604 × τ w mQ (r 2  = 0.9641). Our finding indicates that aortic impulse response can be an effective method for the estimation of arterial τ w by using a single pressure recording together with the assumed Q tri .

Decreased expression of fibulin-4 in aortic wall of aortic dissection.

PubMed

Huawei, P; Qian, C; Chuan, T; Lei, L; Laing, W; Wenlong, X; Wenzhi, L

2014-02-01

In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

Preservation of the bicuspid aortic valve.

PubMed

Schäfers, Hans-Joachim; Aicher, Diana; Langer, Frank; Lausberg, Henning F

2007-02-01

Bicuspid anatomy of the aortic valve is a common reason for aortic regurgitation and is associated with aortic dilatation in more than 50% of patients. We have observed different patterns of aortic dilatation and used different approaches preserving the valve. Between October 1995 and February 2006, a regurgitant bicuspid valve was repaired in 173 patients. The aorta was normal in 57 patients who underwent isolated repair. Aortic dilatation mainly above commissural level (n = 38) was treated by separate valve repair plus supracommissural aortic replacement. In 78 patients, aortic dilatation involved the root and was treated by root remodeling. Hospital mortality and perioperative morbidity were low in all three groups. Myocardial ischemia was significantly shorter in repair plus aortic replacement than remodeling (p < 0.001). Freedom from aortic regurgitation II or greater at 5 years varied between 91% and 96%. Freedom from reoperation at 5 years was 97% after remodeling, but only 53% after repair plus aortic replacement (p = 0.33). Symmetric prolapse was the most frequent cause for reoperation. The long-term stability of bicuspid aortic valve repair is excellent in the absence of aortic pathology. In the presence of aortic dilatation, root remodeling leads to equally stable valve durability. In patients with less pronounced root dilatation, separate valve repair plus aortic replacement may be a less complex alternative. Symmetric prolapse should be avoided if the ascending aorta is replaced.

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

PubMed

Matsumura, Y; Tsukahara, Y; Kojima, T; Murata, S; Murakami, A; Takada, K; Takaoka, M; Morimoto, S

1995-03-01

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional distribution of circumferential residual strains in the human aorta according to age and gender.

PubMed

Sokolis, Dimitrios P; Savva, Giannis D; Papadodima, Stavroula A; Kourkoulis, Stavros K

2017-03-01

The biomechanical response of the human aorta varies with axial location, but little is known about the respective variation of residual strains. Such data are available for common lab animals, but in the traditional opening angle measurement the aorta is considered as an ideal cylinder and average residual strains are measured, so that the spatial variations of local residual strains are not determined. The present study provides opening angle and residual strain data throughout the course and around the circumference of the aorta harvested during autopsy. Opening angle showed notable topographical variation; the highest value was at the top of aortic arch, declining abruptly toward the ascending aorta and to a near-constant value in the descending aorta, and rising in the abdominal aorta. The variation of curvature and of external but not internal residual stretch resembled that of opening angle. Extensive residual stress and wall thickness differences were evidenced among quadrants, with the more pre-stressed being also the thicker quadrants. Gender had overall minor effects, but aging led to increased parameters, occurring earlier in the distal aorta but at later stages becoming predominant proximally. Differences in caliber were pronounced in older subjects, unlike those in opening angle, residual stretches, and thickness that were striking in middle-aged subjects. By contrast, curvature decreased with aging in relation to the smaller percentwise opening angle differences. Detailed knowledge of the zero-stress/no-load geometry of the human aortic wall is critical for an in-depth understanding of aortic physiology, while providing the basis for comparison with disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

ClinicalTrials.gov

2017-04-26

Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

A novel approach: trans-ascending aorta balloon aortic valvuloplasty via sternotomy for treating severe valvular aortic stenosis in a low-weight infant.

PubMed

Gao, Lei; Wu, Qin; Xu, Xinhua; Zhao, Tianli; Jin, Wancun; Yang, Yifeng

2014-02-01

Severe congenital aortic stenosis in infants is a life-threatening congenital heart anomaly that is typically treated using percutaneous balloon aortic valvuloplasty. The usual route is the femoral artery under radiographic guidance. However, this procedure may be limited by the small size of the femoral artery in low-weight infants. An infant weighing only 7 kg with severe aortic stenosis (peak gradient was 103 mmHg) was successfully treated with a novel approach, that is trans-ascending aorta balloon aortic valvuloplasty guided by transesophageal echocardiography. The patient tolerated the procedure well, and no major complications developed. After the intervention, transesophageal echocardiography indicated a significant reduction of the aortic valvular peak gradient from 103 mmHg to 22 mmHg, no aortic regurgitation was found. Eighteen months after the intervention, echocardiography revealed that the aortic valvular peak gradient had increased to 38 mmHg and that still no aortic regurgitation had occurred. In our limited experience, trans-ascending aorta balloon aortic valvuloplasty for severe aortic stenosis under transesophageal echocardiography guidance effectively reduces the aortic peak gradient. As this is a new procedure, long-term follow up and management will need to be established. It may be an alternative technique to treat congenital aortic stenosis in low-weight patients.

SUBCOMMISSURAL IMPLANTATION OF AORTIC PROSTHESES WITH THE USE OF THE NONCORONARY SINUS AND THE FIBROUS TRIGONES

PubMed Central

Liotta, Domingo; Haller, Jordan D.; Pisanu, Amadeo; Bracco, Daniel; Bertolozzi, Enrique

1979-01-01

The technique described here permits insertion of a large prosthesis into a small aortic annulus and avoids the necessity of additional procedures for enlarging the aortic ring. Inspection of the fibrous skeleton of the heart reveals that the large intervalvular trigone and the noncoronary sinus of Valsalva are remarkably elastic. Full advantage of this natural elasticity is achieved by suturing the prosthesis to the base of these structures from outside the aorta. Sutures are placed in the sinuses of the right and left cusps in the usual manner. Judicious application of this procedure allows the implantation of a No. 23 or No. 24 prosthesis in cases that would require a No. 19 or No. 21 with the use of conventional methods. Images PMID:15216322

Hemodynamics of physiological blood flow in the aorta with nonlinear anisotropic heart valve

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Gilmanov, Anvar; Stolarski, Henryk

2016-11-01

The hemodynamic blood flow in cardiovascular system is one of the most important factor, which causing several vascular diseases. We developed a new Curvilinear Immersed Boundary - Finite Element - Fluid Structure Interaction (CURVIB-FE-FSI) method to analyze hemodynamic of pulsatile blood flow in a real aorta with nonlinear anisotropic aortic valve at physiological conditions. Hyperelastic material model, which is more realistic for describing heart valve have been incorporated in the CURVIB-FE-FSI code to simulate interaction of aortic heart valve with pulsatile blood flow. Comparative studies of hemodynamics for linear and nonlinear models of heart valve show drastic differences in blood flow patterns and hence differences of stresses causing impact at leaflets and aortic wall. This work is supported by the Lillehei Heart Institute at the University of Minnesota.

Double aortic arch

MedlinePlus

Aortic arch anomaly; Double arch; Congenital heart defect - double aortic arch; Birth defect heart - double aortic arch ... aorta is a single arch that leaves the heart and moves leftward. In double aortic arch, some ...

Telemetric ambulatory arterial stiffness index, a predictor of cardio-cerebro-vascular mortality, is associated with aortic stiffness-determining factors.

PubMed

Li, Zhi-Yong; Xu, Tian-Ying; Zhang, Sai-Long; Zhou, Xiao-Ming; Xu, Xue-Wen; Guan, Yun-Feng; Lo, Ming; Miao, Chao-Yu

2013-09-01

Ambulatory arterial stiffness index (AASI) has been proposed as a new measure of arterial stiffness for predicting cardio-cerebro-vascular morbidity and mortality. However, there has been no research on the direct relationships between AASI and arterial stiffness-determining factors. We utilized beat-to-beat intra-aortic blood pressure (BP) telemetry to characterize AASI in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). By determination of aortic structural components and analysis of their correlations with AASI, we provided the first direct evidence for the associations between AASI and arterial stiffness-determining factors including the collagen content and collagen/elastin. Ambulatory arterial stiffness index was positively correlated with pulse pressure in both WKY and SHR, less dependent on BP and BP variability than pulse pressure, and relatively stable, especially the number of BP readings not less than ~36. The correlations between AASI and aortic components were comparable for various AASI values derived from BP readings not less than ~36. Not only AASI but also BP variability and pulse pressure demonstrated a direct relationship with arterial stiffness. These findings indicate AASI may become a routine measure in human arterial stiffness assessment. It is recommended to use a cluster of parameters such as AASI, BP variability, and pulse pressure for evaluating arterial stiffness. © 2013 John Wiley & Sons Ltd.

Finite element analysis of helical flows in human aortic arch: A novel index

PubMed Central

Lee, Cheng-Hung; Liu, Kuo-Sheng; Jhong, Guan-Heng; Liu, Shih-Jung; Hsu, Ming-Yi; Wang, Chao-Jan; Hung, Kuo-Chun

2014-01-01

This study investigates the helical secondary flows in the aortic arch using finite element analysis. The relationship between helical flow and the configuration of the aorta in patients of whose three-dimensional images constructed from computed tomography scans was examined. A finite element model of the pressurized root, arch, and supra-aortic vessels was developed to simulate the pattern of helical secondary flows. Calculations indicate that most of the helical secondary flow was formed in the ascending aorta. Angle α between the zero reference point and the aortic ostium (correlation coefficient (r) = −0.851, P = 0.001), the dispersion index of the cross section of the ascending (r = 0.683, P = 0.021) and descending aorta (r = 0.732, P = 0.010), all correlated closely with the presence of helical flow (P < 0.05). Stepwise multiple linear regression analysis confirmed angel α to be independently associated with the helical flow pattern in therein (standardized coefficients = −0.721, P = 0.023). The presence of helical fluid motion based on the atherosclerotic risks of patients, including those associated with diabetes, hypertension, hyperlipidemia, or renal insufficiency, was also evaluated. Numerical simulation of the flow patterns in aortas incorporating the atherosclerotic risks may better explain the mechanism of formation of helical flows and provide insight into causative factors that underlie them. PMID:24803960

Transcatheter heart valves for the treatment of aortic stenosis: state-of-the-art.

PubMed

Del Valle-Fernández, R; Ruiz, C E

2008-10-01

Degenerative aortic stenosis is the most frequent heart valve disease. As an alternative to surgical aortic valve replacement, several companies are working on the development of new prosthesis designed to be deployed by transcatheter approaches. Both transfemoral and transapical techniques are feasible, and initial trials in high-risk patients show good procedural outcomes and mid-term (up to 2 years) functionality. Two first-generation prosthesis (Edwards-SAPIEN and CoreValve Revalving System) are commercially available in Europe, and a number of other second-generation valves (with the capabilities of repositioning and retrievability) are under evaluation. Among them, the Sadra-Lotus Valve, The Direct Flow Medical valve and the Paniagua Heart Valve have published first-in-man results; the JenaValve and AorTx devices have also been temporarily implanted in humans. The development of repositionable and retrievable prosthesis with improved profile is mandatory, and it is the main focus of current projects. Not only technical improvements but also operators specialization and an optimal patient selection are essential to improve these initial Some procedural challenges need to be overcome prior to the expansion of these techniques to lower risk groups, and time is needed for detailed long-term outcomes and risk estimations. Only with a close collaboration among different specialists, basic researchers and the industry will the future development of transcatheter aortic implantation techniques be ensured.

Noninvasive Evaluation of Varying Pulse Pressures in vivo Using Brachial Sphymomanometry, Applanation Tonometry, and Pulse Wave Ultrasound Manometry.

PubMed

Li, Ronny X; Ip, Ada; Sanz-Miralles, Elena; Konofagou, Elisa E

2017-06-01

The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r 2 < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r 2 = 0.68 and 0.87, respectively). PWUM provides a low-cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites.

Degree of fusiform dilatation of the proximal descending aorta in type B acute aortic dissection can predict late aortic events.

PubMed

Marui, Akira; Mochizuki, Takaaki; Koyama, Tadaaki; Mitsui, Norimasa

2007-11-01

Predicting the risk factors for late aortic events in patients with type B acute aortic dissection without complications may help to determine a therapeutic strategy for this disorder. We investigated whether late aortic events in type B acute aortic dissection can be predicted accurately by an index that expresses the degree of fusiform dilatation of the proximal descending aorta during the acute phase; this index can be calculated as follows: (maximum diameter of the proximal descending aorta)/(diameter of the distal aortic arch + diameter of the descending aorta at the pulmonary artery level). Patients with type B acute aortic dissection without complications (n = 141) were retrospectively analyzed to determine the predictors of late aortic events; these include aortic dilatation, rupture, refractory pain, organ ischemia, rapid aortic enlargement, and rapid enlargement of ulcer-like projections. The fusiform index in patients with late aortic events (0.59) was higher than that in patients without late aortic events (0.53, P < .01). Patients with a higher fusiform index exhibited aortic dilatation earlier than those with a lower fusiform index. By multivariate analysis, we conclude that the predominant independent predictors of late aortic events were a maximum aortic diameter of 40 mm or more, a patent false lumen, and a fusiform index of 0.64 or more (hazard ratios, 3.18, 2.64, and 2.73, respectively). The values of actuarial freedom from aortic events for patients with all 3 predictors at 1, 5, and 10 years were 22%, 17%, and 8%, respectively, whereas the values in those without these predictors were 97%, 94%, and 90%, respectively. The degree of fusiform dilatation of the proximal descending aorta, a patent false lumen, and a large aortic diameter can be predominant predictors of late aortic events in patients with type B acute aortic dissection. Patients with these predictors should be recommended to undergo early interventions (surgery or stent-graft implantation) or at least be closely followed up during the chronic phase before such events develop.

Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B Aortic Dissection with Severe Limb Ischemia.

PubMed

Higuchi, Yoshiro; Tochii, Masato; Takami, Yoshiyuki; Kobayashi, Akihiro; Yanagisawa, Tsutomu; Amano, Kentaro; Sakurai, Yusuke; Ishida, Michiko; Ishikawa, Hiroshi; Hattori, Koji; Takagi, Yasushi

2017-03-24

We report a rare case of retrograde Stanford type A aortic dissection after endovascular repair for complicated Stanford type B aortic dissection. A 45-year-old man presented with a sudden onset of back pain and was transferred to our hospital. Computed tomography demonstrated acute Stanford type B aortic dissection with lower limb ischemia. Emergency endovascular surgery was planned for repair of the Stanford type B aortic dissection. The patient suddenly developed recurrent chest pain 10 days after the initial procedure. Computed tomography revealed retrograde Stanford type A aortic dissection involving the ascending aorta and aortic arch. The patient underwent a successful emergency total aortic arch replacement.

Metabolism of native and naturally occurring multiple modified low density lipoprotein in smooth muscle cells of human aortic intima.

PubMed

Tertov, V V; Orekhov, A N

1997-01-01

The subfraction of low density lipoprotein (LDL) with low sialic acid content that caused accumulation of cholesterol esters in human aortic smooth muscle cells has been found in the blood of coronary atherosclerosis patients. It was demonstrated that this subfraction consists of LDL with small size, high electronegative charge, reduced lipid content, altered tertiary structure of apolipoprotein B, etc. LDL of this subfraction is naturally occurring multiple-modified LDL (nomLDL). In this study we compared the binding, uptake and proteolytic degradation of native LDL and nomLDL by smooth muscle cells cultured from human grossly normal intima, fatty streaks, and atherosclerotic plaques. Uptake of nomLDL by normal and atherosclerotic cells was 3.5- and 6-fold, respectively, higher than uptake of native LDL. Increased uptake of nomLDL was due to increased binding of this LDL by intimal smooth muscle cells. The enhanced binding is explained by the interaction of nomLDL with cellular receptors other than LDL-receptor. Modified LDL interacted with the scavenger receptor, asialoglycoprotein receptor, and also with cell surface proteoglycans. Rates of degradation of nomLDL were 1.5- and 5-fold lower than degradation of native LDL by normal and atherosclerotic cells, respectively. A low rate of nomLDL degradation was also demonstrated in homogenates of intimal cells. Activities of lysosomal proteinases of atherosclerotic cells were decreased compared with normal cells. Pepstatin A, a cathepsin D inhibitor, completely inhibited lipoprotein degradation, while serine, thiol, or metallo-proteinase inhibitors had partial effect. This fact reveals that cathepsin D is involved in initial stages of apoB degradation by intimal smooth muscle cells. Obtained data show that increased uptake and decreased lysosomal degradation of nomLDL may be the main cause of LDL accumulation in human aortic smooth muscle cells, leading to foam cell formation.

Alpha1B-adrenoceptor signaling and cell motility: GTPase function of Gh/transglutaminase 2 inhibits cell migration through interaction with cytoplasmic tail of integrin alpha subunits.

PubMed

Kang, Sung Koo; Yi, Kye Sook; Kwon, Nyoun Soo; Park, Kwang-Hyun; Kim, Uh-Hyun; Baek, Kwang Jin; Im, Mie-Jae

2004-08-27

A multifunctional enzyme, G(h), is a GTP-binding protein that couples to the alpha(1B)-adrenoreceptor and stimulates phospholipase C-delta1 but also displays transglutaminase 2 (TG2) activity. G(h)/TG2 has been implicated to play a role in cell motility. In this study we have examined which function of G(h)/TG2 is involved in this cellular response and the molecular basis. Treatment of human aortic smooth muscle cell with epinephrine inhibits migration to fibronectin and vitronectin, and the inhibition is blocked by the alpha(1)-adrenoreceptor antagonist prazosin or chloroethylclonidine. Up-regulation or overexpression of G(h)/TG2 in human aortic smooth muscle cells, DDT1-MF2, or human embryonic kidney cells, HEK 293 cells, results in inhibition of the migratory activity, and stimulation of the alpha(1B)-adrenoreceptor with the alpha(1) agonist further augments the inhibition of migration of human aortic smooth muscle cells and DDT1-MF2. G(h)/TG2 is coimmunoprecipitated by an integrin alpha(5) antibody and binds to the cytoplasmic tail peptide of integrins alpha(5), alpha(v), and alpha(IIb) subunits in the presence of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS). Mutation of Lys-Arg residues in the GFFKR motif, present in the alpha(5)-tail, significantly reduces the binding of GTPgammaS-G(h)/TG2. Moreover, the motif-containing integrin alpha(5)-tail peptides block G(h)/TG2 coimmunoprecipitation and reverse the inhibition of the migratory activity of HEK 293 cells caused by overexpression G(h)/TG2. These results provide evidence that G(h) function initiates the modulation of cell motility via association of GTP-bound G(h)/TG2 with the GFFKR motif located in integrin alpha subunits.

Impaired Collagen Biosynthesis and Cross‐linking in Aorta of Patients With Bicuspid Aortic Valve

PubMed Central

Wågsäter, Dick; Paloschi, Valentina; Hanemaaijer, Roeland; Hultenby, Kjell; Bank, Ruud A.; Franco‐Cereceda, Anders; Lindeman, Jan H. N.; Eriksson, Per

2013-01-01

Background Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysm. In the present study, collagen homeostasis in nondilated and dilated aorta segments from patients with BAV was studied, with normal and dilated aortas from tricuspid aortic valve (TAV) patients as reference. Methods and Results Ascending aortas from 56 patients were used for biochemical and morphological analyses of collagen. mRNA expression was analyzed in 109 patients. Collagen turnover rates were similar in nondilated and dilated aortas of BAV patients, showing that aneurysmal formation in BAV is, in contrast to TAV, not associated with an increased collagen turnover. However, BAV in general was associated with an increased aortic collagen turnover compared with nondilated aortas of TAV patients. Importantly, the ratio of hydroxylysyl pyridinoline (HP) to lysyl pyridinoline (LP), 2 distinct forms of collagen cross‐linking, was lower in dilated aortas from patients with BAV, which suggests that BAV is associated with a defect in the posttranslational collagen modification. This suggests a deficiency at the level of lysyl hydroxylase (PLOD1), which was confirmed by mRNA and protein analyses that showed reduced PLOD1 expression but normal lysyl oxidase expression in dilated aortas from patients with BAV. This suggests that impaired collagen cross‐linking in BAV patients may be attributed to changes in the expression and/or activity of PLOD1. Conclusions Our results demonstrate an impaired biosynthesis and posttranslational modification of collagen in aortas of patients with BAV, which may explain the increased aortic aneurysm formation in BAV patients. PMID:23525417

The effects of contrast media volume on acute kidney injury after transcatheter aortic valve replacement: a systematic review and meta-analysis.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Podboy, Alexander J; Gillaspie, Erin A; Greason, Kevin L; Kashani, Kianoush B

2016-11-01

The goal of this systematic review was to assess the effects of contrast media volume on transcatheter aortic valve replacement-related acute kidney injury. A literature search was performed using Medline, EMbase, the Cochrane Database of Systematic Reviews, and clinicaltrials.gov from the inception of these databases through December 2015. Studies that reported relative risk, odds ratio, or hazard ratio comparing the risks of acute kidney injury following transcatheter aortic valve replacement in patients who received high contrast media volume were included. Pooled risk ratio (RR) and 95% confidence intervals (95% CI) were calculated using a random-effect, generic inverse variance method. Four cohort studies composed of 891 patients were included in the analyses to assess the risk of acute kidney injury after transcatheter aortic valve replacement in patients who received high contrast media volume. The pooled RR of acute kidney injury after transcatheter aortic valve replacement in patients who received a large volume of contrast media was 1.41 (95% CI, 0.87 to 2.28) compared with low contrast media volume. The meta-analysis was limited to studies using standard acute kidney injury definitions, and the pooled RR of acute kidney injury in patients who received high contrast media volume is 1.12 (95% CI, 0.78 to 1.62). Our meta-analysis shows no significant association between contrast media volume and risk of acute kidney injury after transcatheter aortic valve replacement. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Automatic segmentation and co-registration of gated CT angiography datasets: measuring abdominal aortic pulsatility

NASA Astrophysics Data System (ADS)

Wentz, Robert; Manduca, Armando; Fletcher, J. G.; Siddiki, Hassan; Shields, Raymond C.; Vrtiska, Terri; Spencer, Garrett; Primak, Andrew N.; Zhang, Jie; Nielson, Theresa; McCollough, Cynthia; Yu, Lifeng

2007-03-01

Purpose: To develop robust, novel segmentation and co-registration software to analyze temporally overlapping CT angiography datasets, with an aim to permit automated measurement of regional aortic pulsatility in patients with abdominal aortic aneurysms. Methods: We perform retrospective gated CT angiography in patients with abdominal aortic aneurysms. Multiple, temporally overlapping, time-resolved CT angiography datasets are reconstructed over the cardiac cycle, with aortic segmentation performed using a priori anatomic assumptions for the aorta and heart. Visual quality assessment is performed following automatic segmentation with manual editing. Following subsequent centerline generation, centerlines are cross-registered across phases, with internal validation of co-registration performed by examining registration at the regions of greatest diameter change (i.e. when the second derivative is maximal). Results: We have performed gated CT angiography in 60 patients. Automatic seed placement is successful in 79% of datasets, requiring either no editing (70%) or minimal editing (less than 1 minute; 12%). Causes of error include segmentation into adjacent, high-attenuating, nonvascular tissues; small segmentation errors associated with calcified plaque; and segmentation of non-renal, small paralumbar arteries. Internal validation of cross-registration demonstrates appropriate registration in our patient population. In general, we observed that aortic pulsatility can vary along the course of the abdominal aorta. Pulsation can also vary within an aneurysm as well as between aneurysms, but the clinical significance of these findings remain unknown. Conclusions: Visualization of large vessel pulsatility is possible using ECG-gated CT angiography, partial scan reconstruction, automatic segmentation, centerline generation, and coregistration of temporally resolved datasets.

Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

2009-11-01

Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

A method for the computational modeling of the physics of heart murmurs

NASA Astrophysics Data System (ADS)

Seo, Jung Hee; Bakhshaee, Hani; Garreau, Guillaume; Zhu, Chi; Andreou, Andreas; Thompson, William R.; Mittal, Rajat

2017-05-01

A computational method for direct simulation of the generation and propagation of blood flow induced sounds is proposed. This computational hemoacoustic method is based on the immersed boundary approach and employs high-order finite difference methods to resolve wave propagation and scattering accurately. The current method employs a two-step, one-way coupled approach for the sound generation and its propagation through the tissue. The blood flow is simulated by solving the incompressible Navier-Stokes equations using the sharp-interface immersed boundary method, and the equations corresponding to the generation and propagation of the three-dimensional elastic wave corresponding to the murmur are resolved with a high-order, immersed boundary based, finite-difference methods in the time-domain. The proposed method is applied to a model problem of aortic stenosis murmur and the simulation results are verified and validated by comparing with known solutions as well as experimental measurements. The murmur propagation in a realistic model of a human thorax is also simulated by using the computational method. The roles of hemodynamics and elastic wave propagation on the murmur are discussed based on the simulation results.

Fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm media

PubMed Central

Tsamis, Alkiviadis; Phillippi, Julie A.; Koch, Ryan G.; Pasta, Salvatore; D'Amore, Antonio; Watkins, Simon C.; Wagner, William R.; Gleason, Thomas G.; Vorp, David A.

2013-01-01

It was recently demonstrated by our group that the delamination strength of ascending thoracic aortic aneurysms (ATAA) was lower than that of control (CTRL, non-aneurysmal) ascending thoracic aorta (ATA), and the reduced strength was more pronounced among bicuspid (BAV) vs. tricuspid aortic valve (TAV) patients, suggesting a different risk of aortic dissection for BAV patients. We hypothesized that aortic valve morphologic phenotype predicts fiber micro-architectural anomalies in ATA. To test the hypothesis, we characterized the micro-architecture in the longitudinal-radial (Z-RAD) and circumferential-radial (Θ-RAD) planes of human ATA tissue that was artificially dissected medially. The outer and inner-media of CTRL-ATA, BAV-ATAA and TAV-ATAA were imaged using multi-photon microscopy in the Z-RAD and Θ-RAD planes to observe collagen and elastin. Micrographs were processed using an image-based tool to quantify several micro-architectural characteristics. In the outer-media of BAV-ATAA, elastin was more undulated and less aligned about the Θ-axis when compared with CTRL-ATA, which is consistent with increased tensile stretch at inflection point of Θ-strips of adventitial-medial half of BAV-ATAA (1.28) when compared with CTRL-ATA (1.13). With increasing age, collagen became more undulated about the Z-axis within the outer-media of TAV-ATAA, and elastin became more oriented in the Z-axis and collagen less radially-oriented within the inner-media of TAV-ATAA. This discrepancy in the micro-architecture with fibers in the inner layers being more stretched and with disrupted radially-oriented components than fibers in the outer layers may be associated with the development, progression and vascular remodeling in aneurysms arising in TAV patients. PMID:24075403

Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm.

PubMed

Adam, Matti; Kooreman, Nigel; Jagger, Ann; Wagenhaeuser, Markus U; Mehrkens, Dennis; Wang, Yongming; Kayama, Yosuke; Toyama, Kensuke; Raaz, Uwe; Schellinger, Isabel N; Maegdefessel, Lars; Spin, Joshua M; Hamming, Jaap F; Quax, Paul H A; Baldus, Stephan; Wu, Joseph C; Tsao, Philip S

2018-06-07

Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE -/- infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4 + /CD25 + /Foxp3 (forkhead box P3) + regulatory T cells, with fewer CD8 + /Granzyme B + cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of LPS-stimulated and Ang II-primed human peripheral blood mononuclear cells. Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression. © 2018 American Heart Association, Inc.

Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum.

PubMed

Jakobsdottir, Greta; Jädert, Cecilia; Holm, Lena; Nyman, Margareta E

2013-11-14

SCFA are important end products formed during colonic fermentation of dietary fibre (DF). It has been suggested that propionic and butyric acids affect metabolic parameters, low-grade systemic inflammation, insulin resistance and obesity. The aim of the present study was to investigate whether the various SCFA profiles observed after fermentation in the caecum of rats fed pectin, guar gum and fructo-oligosaccharides (FOS) were also represented in hepatic portal and aortic serum. The SCFA in serum were extracted using hollow fibre-supported liquid membrane extraction before GLC analysis. The concentrations of acetic, propionic and butyric acids in caecal content correlated well with those in portal serum (P< 0·001) for all the three diets. A weaker correlation was found for propionic and butyric acids between the caecal content and aortic serum (P< 0·05). Butyric acid concentration in caecal content was also reflected in the aortic serum (P= 0·019) of rats fed FOS. FOS gave rather low amounts of the SCFA, especially butyric acid, but caecal tissue weight was higher with FOS than with the other two diets. This may be explained by rapid fermentation and quick utilisation/absorption of the SCFA. The present study also showed that propionic acid was metabolised/utilised to a higher extent than butyric acid by colonocytes before reaching the liver. We conclude that the formation of propionic and butyric acids in the caecum is reflected by increased concentrations in the aortic blood. This approach may therefore simplify the evaluation and study of SCFA from DF in human subjects.

Pulsatile flows and wall-shear stresses in models simulating normal and stenosed aortic arches

NASA Astrophysics Data System (ADS)

Huang, Rong Fung; Yang, Ten-Fang; Lan, Y.-K.

2010-03-01

Pulsatile aqueous glycerol solution flows in the models simulating normal and stenosed human aortic arches are measured by means of particle image velocimetry. Three transparent models were used: normal, 25% stenosed, and 50% stenosed aortic arches. The Womersley parameter, Dean number, and time-averaged Reynolds number are 17.31, 725, and 1,081, respectively. The Reynolds numbers based on the peak velocities of the normal, 25% stenosed, and 50% stenosed aortic arches are 2,484, 3,456, and 3,931, respectively. The study presents the temporal/spatial evolution processes of the flow pattern, velocity distribution, and wall-shear stress during the systolic and diastolic phases. It is found that the flow pattern evolving in the central plane of normal and stenosed aortic arches exhibits (1) a separation bubble around the inner arch, (2) a recirculation vortex around the outer arch wall upstream of the junction of the brachiocephalic artery, (3) an accelerated main stream around the outer arch wall near the junctions of the left carotid and the left subclavian arteries, and (4) the vortices around the entrances of the three main branches. The study identifies and discusses the reasons for the flow physics’ contribution to the formation of these features. The oscillating wall-shear stress distributions are closely related to the featured flow structures. On the outer wall of normal and slightly stenosed aortas, large wall-shear stresses appear in the regions upstream of the junction of the brachiocephalic artery as well as the corner near the junctions of the left carotid artery and the left subclavian artery. On the inner wall, the largest wall-shear stress appears in the region where the boundary layer separates.

Fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm media.

PubMed

Tsamis, Alkiviadis; Phillippi, Julie A; Koch, Ryan G; Pasta, Salvatore; D'Amore, Antonio; Watkins, Simon C; Wagner, William R; Gleason, Thomas G; Vorp, David A

2013-11-15

It was recently demonstrated by our group that the delamination strength of ascending thoracic aortic aneurysms (ATAA) was lower than that of control (CTRL, non-aneurysmal) ascending thoracic aorta (ATA), and the reduced strength was more pronounced among bicuspid (BAV) vs. tricuspid aortic valve (TAV) patients, suggesting a different risk of aortic dissection for BAV patients. We hypothesized that aortic valve morphologic phenotype predicts fiber micro-architectural anomalies in ATA. To test the hypothesis, we characterized the micro-architecture in the longitudinal-radial (Z-RAD) and circumferential-radial (Θ-RAD) planes of human ATA tissue that was artificially dissected medially. The outer and inner-media of CTRL-ATA, BAV-ATAA and TAV-ATAA were imaged using multi-photon microscopy in the Z-RAD and Θ-RAD planes to observe collagen and elastin. Micrographs were processed using an image-based tool to quantify several micro-architectural characteristics. In the outer-media of BAV-ATAA, elastin was more undulated and less aligned about the Θ-axis when compared with CTRL-ATA, which is consistent with increased tensile stretch at inflection point of Θ-strips of adventitial-medial half of BAV-ATAA (1.28) when compared with CTRL-ATA (1.13). With increasing age, collagen became more undulated about the Z-axis within the outer-media of TAV-ATAA, and elastin became more oriented in the Z-axis and collagen less radially-oriented within the inner-media of TAV-ATAA. This discrepancy in the micro-architecture with fibers in the inner layers being more stretched and with disrupted radially-oriented components than fibers in the outer layers may be associated with the development, progression and vascular remodeling in aneurysms arising in TAV patients. © 2013 Elsevier Ltd. All rights reserved.

Fluid-structure interaction analysis of the flow through a stenotic aortic valve

NASA Astrophysics Data System (ADS)

Maleki, Hoda; Labrosse, Michel R.; Durand, Louis-Gilles; Kadem, Lyes

2009-11-01

In Europe and North America, aortic stenosis (AS) is the most frequent valvular heart disease and cardiovascular disease after systemic hypertension and coronary artery disease. Understanding blood flow through an aortic stenosis and developing new accurate non-invasive diagnostic parameters is, therefore, of primarily importance. However, simulating such flows is highly challenging. In this study, we considered the interaction between blood flow and the valve leaflets and compared the results obtained in healthy valves with stenotic ones. One effective method to model the interaction between the fluid and the structure is to use Arbitrary Lagrangian-Eulerian (ALE) approach. Our two-dimensional model includes appropriate nonlinear and anisotropic materials. It is loaded during the systolic phase by applying pressure curves to the fluid domain at the inflow. For modeling the calcified stenotic valve, calcium will be added on the aortic side of valve leaflets. Such simulations allow us to determine the effective orifice area of the valve, one of the main parameters used clinically to evaluate the severity of an AS, and to correlate it with changes in the structure of the leaflets.

Hemodynamics of the Aortic Jet and Implications for Detection of Aortic Stenosis Murmurs

NASA Astrophysics Data System (ADS)

Zhu, Chi; Seo, Junghee; Bakhshaee, Hani; Mittal, Rajat

2016-11-01

Cardiac auscultation with a stethoscope has served as the primary method for qualitative screening of cardiovascular conditions for over a hundred years. However, a lack of quantitative understanding of the flow mechanism(s) responsible for the generation of the murmurs, as well as the effect of intervening tissue on the propagation of these murmurs has been a significant limiting factor in the advancement of automated cardiac auscultation. In this study, a multiphysics computational modeling approach is used to investigate these issues. Direct numerical simulation (DNS) is used to explore the fluid dynamics of the jets formed at the aortic valve and the pressure fluctuations generated by the interaction of this jet with the aortic wall. Subsequently, structural wave propagation in the tissue is resolved by a high-order, linear viscoelastic wave solver in order to explore the propagation of the murmurs through a tissue-like material. The implications of these results for cardiac auscultation are discussed. The authors would like to acknowledge the financial support from NSF Grants IIS-1344772, CBET-1511200, and computational resource by XSEDE NSF Grant TG-CTS100002.

Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm.

PubMed

Roberts, William Clifford; Vowels, Travis James; Ko, Jong Mi; Filardo, Giovanni; Hebeler, Robert Frederick; Henry, Albert Carl; Matter, Gregory John; Hamman, Baron Lloyd

2011-03-01

There is debate concerning whether an aneurysmal ascending aorta should be replaced when associated with a dysfunctioning aortic valve that is to be replaced. To examine this issue, we divided the patients by type of aortic valve dysfunction-either aortic stenosis (AS) or pure aortic regurgitation (AR)-something not previously undertaken. Of 122 patients with ascending aortic aneurysm (unassociated with aortitis or acute dissection), the aortic valve was congenitally malformed (unicuspid or bicuspid) in 58 (98%) of the 59 AS patients, and in 38 (60%) of the 63 pure AR patients. Ascending aortic medial elastic fiber loss (EFL) (graded 0 to 4+) was zero or 1+ in 53 (90%) of the AS patients, in 20 (53%) of the 38 AR patients with bicuspid valves, and in all 12 AR patients with tricuspid valves unassociated with the Marfan syndrome. An unadjusted analysis showed that, among the 96 patients with congenitally malformed valves, the 38 AR patients had a significantly higher likelihood of 2+ to 4+ EFL than the 58 AS patients (crude odds ratio: 8.78; 95% confidence interval: 2.95, 28.13). These data strongly suggest that the type of aortic valve dysfunction-AS versus pure AR-is very helpful in predicting loss of aortic medial elastic fibers in patients with ascending aortic aneurysms and aortic valve disease.

A Lagrangian cylindrical coordinate system for characterizing dynamic surface geometry of tubular anatomic structures.

PubMed

Lundh, Torbjörn; Suh, Ga-Young; DiGiacomo, Phillip; Cheng, Christopher

2018-03-03

Vascular morphology characterization is useful for disease diagnosis, risk stratification, treatment planning, and prediction of treatment durability. To quantify the dynamic surface geometry of tubular-shaped anatomic structures, we propose a simple, rigorous Lagrangian cylindrical coordinate system to monitor well-defined surface points. Specifically, the proposed system enables quantification of surface curvature and cross-sectional eccentricity. Using idealized software phantom examples, we validate the method's ability to accurately quantify longitudinal and circumferential surface curvature, as well as eccentricity and orientation of eccentricity. We then apply the method to several medical imaging data sets of human vascular structures to exemplify the utility of this coordinate system for analyzing morphology and dynamic geometric changes in blood vessels throughout the body. Graphical abstract Pointwise longitudinal curvature of a thoracic aortic endograft surface for systole and diastole, with their absolute difference.

Effectiveness of open versus endovascular abdominal aortic aneurysm repair in population settings: A systematic review of statewide databases.

PubMed

Williams, Christopher R; Brooke, Benjamin S

2017-10-01

Patient outcomes after open abdominal aortic aneurysm and endovascular aortic aneurysm repair have been widely reported from several large, randomized, controlled trials. It is not clear whether these trial outcomes are representative of abdominal aortic aneurysm repair procedures performed in real-world hospital settings across the United States. This study was designed to evaluate population-based outcomes after endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair using statewide inpatient databases and examine how they have helped improve our understanding of abdominal aortic aneurysm repair. A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify articles comparing endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using data from statewide inpatient databases. This search was limited to studies published in the English language after 1990, and abstracts were screened and abstracted by 2 authors. Our search yielded 17 studies published between 2004 and 2016 that used data from 29 different statewide inpatient databases to compare endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. These studies support the randomized, controlled trial results, including a lower mortality associated with endovascular aortic aneurysm repair extended from the perioperative period up to 3 years after operation, as well as a higher complication rate after endovascular aortic aneurysm repair. The evidence from statewide inpatient database analyses has also elucidated trends in procedure volume, patient case mix, volume-outcome relationships, and health care disparities associated with endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. Population analyses of endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using statewide inpatient databases have confirmed short- and long-term mortality outcomes obtained from large, randomized, controlled trials. Moreover, these analyses have allowed us to assess the effect of endovascular aortic aneurysm repair adoption on population outcomes and patient case mix over time. Published by Elsevier Inc.

Trends in aortic aneurysm- and dissection-related mortality in the state of São Paulo, Brazil, 1985–2009: multiple-cause-of-death analysis

PubMed Central

2012-01-01

Background Aortic aneurysm and dissection are important causes of death in older people. Ruptured aneurysms show catastrophic fatality rates reaching near 80%. Few population-based mortality studies have been published in the world and none in Brazil. The objective of the present study was to use multiple-cause-of-death methodology in the analysis of mortality trends related to aortic aneurysm and dissection in the state of Sao Paulo, between 1985 and 2009. Methods We analyzed mortality data from the Sao Paulo State Data Analysis System, selecting all death certificates on which aortic aneurysm and dissection were listed as a cause-of-death. The variables sex, age, season of the year, and underlying, associated or total mentions of causes of death were studied using standardized mortality rates, proportions and historical trends. Statistical analyses were performed by chi-square goodness-of-fit and H Kruskal-Wallis tests, and variance analysis. The joinpoint regression model was used to evaluate changes in age-standardized rates trends. A p value less than 0.05 was regarded as significant. Results Over a 25-year period, there were 42,615 deaths related to aortic aneurysm and dissection, of which 36,088 (84.7%) were identified as underlying cause and 6,527 (15.3%) as an associated cause-of-death. Dissection and ruptured aneurysms were considered as an underlying cause of death in 93% of the deaths. For the entire period, a significant increased trend of age-standardized death rates was observed in men and women, while certain non-significant decreases occurred from 1996/2004 until 2009. Abdominal aortic aneurysms and aortic dissections prevailed among men and aortic dissections and aortic aneurysms of unspecified site among women. In 1985 and 2009 death rates ratios of men to women were respectively 2.86 and 2.19, corresponding to a difference decrease between rates of 23.4%. For aortic dissection, ruptured and non-ruptured aneurysms, the overall mean ages at death were, respectively, 63.2, 68.4 and 71.6 years; while, as the underlying cause, the main associated causes of death were as follows: hemorrhages (in 43.8%/40.5%/13.9%); hypertensive diseases (in 49.2%/22.43%/24.5%) and atherosclerosis (in 14.8%/25.5%/15.3%); and, as associated causes, their principal overall underlying causes of death were diseases of the circulatory (55.7%), and respiratory (13.8%) systems and neoplasms (7.8%). A significant seasonal variation, with highest frequency in winter, occurred in deaths identified as underlying cause for aortic dissection, ruptured and non-ruptured aneurysms. Conclusions This study introduces the methodology of multiple-causes-of-death to enhance epidemiologic knowledge of aortic aneurysm and dissection in São Paulo, Brazil. The results presented confer light to the importance of mortality statistics and the need for epidemiologic studies to understand unique trends in our own population. PMID:23046791

NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells.

PubMed

Park, Il Hwan; Hwang, Hye Mi; Jeon, Byeong Hwa; Kwon, Hyung-Joo; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

2015-06-12

Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-θ (PKCθ) and protein kinase C-β (PKCβ) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCθ and PKCβ stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox(-/-) mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.

Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

PubMed

Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

2016-04-01

Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography: Feasibility as a Sensitive Method for Monitoring Bicuspid Aortic Valve Aortopathy.

PubMed

Trinh, Brian; Dubin, Iram; Rahman, Ozair; Ferreira Botelho, Marcos P; Naro, Nicholas; Carr, James C; Collins, Jeremy D; Barker, Alex J

2017-04-01

Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth. A retrospective, institutional review board-approved, and Health Insurance Portability and Accountability Act-compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P < 0.05, significant). The diameter of maximal growth (DMG), defined as the diameter at SOV or MAA with the faster growth rate, was recorded. The mean time of follow-up was 2.6 ± 0.82 years. The intraobserver COV was 0.01 for SOV, 0.02 for MAA, and 0.02 for volume (interobserver COV: 0.02, 0.03, 0.04, respectively). The ICC was 0.83 for SOV, 0.86 for MAA, 0.90 for DMG, and 0.95 for volume. Average aortic measurements at baseline and (follow-up) were 42 ± 3 mm (42 ± 3 mm, P = 0.11) at SOV, 46 ± 4 mm (47 ± 4 mm, P < 0.05) at MAA, and 130 ± 23 mL (144 ± 24 mL, P < 0.05). Average size changes were 0.2 ± 0.6 mm/y (1% ± 2%) at SOV, 0.5 ± 0.8 mm/y (1% ± 2%) at MAA, 0.7 ± 0.7 mm/y (2% ± 2%) at DMG, and 6 ± 3 mL/y (4% ± 3%) with volumetry. Three-dimensional CEMRA volumetry exhibited a larger effect when examining percentage growth, a better ICC, and a marginally lower COV. Volumetry may be more sensitive to growth and possibly less affected by error than diameter measurements.

Coil embolization of an aneurysmal type B dissection persistent false lumen after visceral hybrid repair.

PubMed

Riga, Celia; Bicknell, Colin; Jenkins, Michael; Hamady, Mohamad

2009-01-01

Complex aortic dissections with subsequent dilatation may be managed by using a visceral hybrid approach. In some cases, however, there is substantial retrograde blood flow into the false lumen, leaving a pressurized aneurysmal segment. The authors describe a novel treatment method whereby successful seal of a distal type 1 endoleak was achieved with coil embolization and a liquid injectable embolic agent. The patient was followed up for 2 years without further aortic dilatation or complications.

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report.

PubMed

Kamran, Mudassar; Fowler, Kathryn J; Mellnick, Vincent M; Sicard, Gregorio A; Narra, Vamsi R

2016-06-01

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.

Vasorelaxant Action of the Chloroform Fraction of Orthosiphon stamineus via NO/cGMP Pathway, Potassium and Calcium Channels.

PubMed

Yam, Mun Fei; Tan, Chu Shan; Ahmad, Mariam; Ruan, Shibao

2016-01-01

Orthosiphon stamineus Benth. (Lamiaceae) is an important plant in traditional folk medicine that is used to treat hypertension and kidney stones. In humans, this plant has been tested as an addition regiment for antihypertensive treatment. Among the treatments for hypertension, O. stamineus had been to have diuretic and vasorelaxant effects in animal models. There is still very little information regarding the vasorelaxant effect of O. stamineus. Therefore, the present study was designed to investigate the vasorelaxant activity and mechanism of action of the fractions of O. stamineus. The vasorelaxant activity and the underlying mechanisms of the chloroform fraction of the 50% methanolic extract of O. stamineus (CF) was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. CF caused relaxation of the aortic ring pre-contracted with phenylephrine in the presence and absence of endothelium, and pre-contracted with potassium chloride in endothelium-intact aortic ring. In the presence of endothelium, both indomethacin (a nonselective cyclooxygenase inhibitor) and [Formula: see text]-[1,2,4]Oxadiazolo[4,3-[Formula: see text

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model.

PubMed

Poullis, Michael P; Warwick, Richard; Oo, Aung; Poole, Robert J

2008-06-01

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With Bicuspid Aortic Valve and a Dilated Ascending Aorta.

PubMed

Masri, Ahmad; Kalahasti, Vidyasagar; Svensson, Lars G; Alashi, Alaa; Schoenhagen, Paul; Roselli, Eric E; Johnston, Douglas R; Rodriguez, L Leonardo; Griffin, Brian P; Desai, Milind Y

2017-06-01

In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height. We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm 2 /m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6-12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20-3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26-0.80) was associated with improved survival (both P <0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio. In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death. © 2017 American Heart Association, Inc.

Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults.

PubMed

Hughes, William E; Ueda, Kenichi; Treichler, David P; Casey, Darren P

2016-09-30

Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

The Provisional Extension To Induce Complete Attachment (PETTICOAT) technique to promote distal aortic remodelling in repair of acute DeBakey type I aortic dissection: preliminary results.

PubMed

Hsu, Hung-Lung; Chen, Yin-Yin; Huang, Chun-Yang; Huang, Jih-Hsin; Chen, Jer-Shen

2016-07-01

To report our preliminary results of an aggressive technique, the Provisional Extension To Induce Complete Attachment (PETTICOAT), in repair of acute DeBakey type I aortic dissection. From April 2014 to November 2014, 18 patients with acute DeBakey type I aortic dissection were reviewed retrospectively. Nine patients underwent open repair combined with proximal stent grafting and distal bare stenting (PETTICOAT group). For comparison, another 9 patients underwent open repair combined with proximal stent grafting (NON-PETTICOAT group) were included. Open repair entailed ascending aorta plus total arch replacement under circulatory arrest, with variable aortic root work. Mortality and morbidity were recorded, and computed tomography was performed to evaluate the aortic remodelling at 6 months postoperatively. Preoperative parameters were similar. In the PETTICOAT group, one early mortality was noted. One complication of cardiac tamponade and sternal wound infection led to reopen surgeries. In the NON-PETTICOAT group, one case of transient ischaemic attack took place. Compared with the NON-PETTICOAT group, a significant increase in diameter of true lumen (median, 0.6 vs 0.1 mm, P < 0.01) and a decrease in diameter of false lumen (FL; median, -0.9 vs 0.0 mm, P < 0.01) at the level of lowest renal artery were noted in the PETTICOAT group. Moreover, significant FL volume regression (median, -102.0 vs -42.2 mm(3), P = 0.03) was observed in the PETTICOAT group. More cases of total thrombosis or regression of FL down to the level of renal artery were also noted in the PETTICOAT group (5/8 vs 0/9, P < 0.01). Two patients of the NON-PETTICOAT group received endovascular distal aortic reintervention at 6 months. The PETTICOAT technique in the management of acute DeBakey type I dissection is a feasible and promising method to promote distal aortic remodelling. However, outcomes are preliminary and further follow-up is required. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Acute aortic dissection involving the root: operative and long-term outcome after curative proximal repair†

PubMed Central

Urbanski, Paul P.; Lenos, Aristidis; Irimie, Vadim; Bougioukakis, Petros; Zacher, Michael; Diegeler, Anno

2016-01-01

OBJECTIVES The aim of the study was to evaluate operative and long-term results after surgery of acute aortic dissection involving the root, in which the proximal repair consisted of curative resection of all dissected aortic sinuses and was performed using either valve-sparing root repair or complete root replacement with a valve conduit. METHODS Between August 2002 and March 2013, 162 consecutive patients (mean age 63 ± 14 years) underwent surgery for acute type A aortic dissection. Eighty-six patients with an involvement of the aortic root underwent curative surgery of the proximal aorta consisting of valve-sparing root repair (n = 54, 62.8%) or complete valve and root replacement using composite valve grafts (n = 32, 37.2%). In patients with root repair, all dissected aortic walls were resected and root remodelling using the single patch technique (n = 53) or root repair with valve reimplantation (n = 1) was performed without the use of any glue. All perioperative data were collected prospectively and retrospective statistical examination was performed using univariate and multivariate analyses. RESULTS The mean follow-up was 5.2 ± 3.5 years for all patients (range 0–12 years) and 6.1 ± 3.3 years for survivors. The 30-day mortality rate was 5.8% (5 patients), being considerably lower in the repair sub-cohort (1.9 vs 12.5%). The estimated survival rate at 5 and 10 years was 80.0 ± 4.5 and 69.1 ± 6.7%, respectively. No patient required reoperation on the proximal aorta and/or aortic valve during the follow-up time and there were only two valve-related events (both embolic, one in each group). Among those patients with repaired valves, the last echocardiography available showed no insufficiency in 40 and an irrelevant insufficiency (1+) in 14. CONCLUSIONS Curative repair of the proximal aorta in acute dissection involving the root provides favourable operative and long-term outcome with very low risk of aortic complications and/or reoperations, regardless if a valve-sparing procedure or replacement with a valve conduit is used. Valve-sparing surgery is frequently suitable, providing excellent outcome and very high durability. PMID:26848190

The effect of proximal anastomosis on the expansion rate of a dilated ascending aorta in coronary artery bypass surgery: a prospective study

PubMed Central

Balcı, Ahmet Yavuz; Vural, Unsal; Özdemir, MD Fatih; Kızılay, Mehmet; Şenocak, Mutlu; Kayacıoğlu, Ilyas; Yekeler, Ibrahim; Aksoy, Rezan; Satılmış,, Seçkin; Şaşkın, Huseyin

2017-01-01

Summary Background: This study was designed to determine the short- and long-term effects of proximal aortic anastomosis, performed during isolated coronary artery bypass grafting (CABG) in patients with dilatation of the ascending aorta who did not require surgical intervention. Methods: The study was performed on 192 (38 female and 160 male patients; mean age, 62.1 ± 9.2 years; range, 42–80 years) patients with dilatation of the ascending aorta who underwent CABG surgery between 1 June 2006 and 31 May 2014. In group 1 (n = 114), the saphenous vein and left internal mammarian artery grafts were used, and proximal anastomosis was performed on the ascending aorta. In group 2 (n = 78), left and right internal mammarian artery grafts were used, and proximal aortic anastomosis was not performed. Pre-operatively and in the first and third years postoperatively, the ascending aortic diameter was measured and recorded using transthoracic echocardiography at four different regions (annulus, sinus of Valsalva, sinotubular junction and tubular aorta). Results: A statistically significant difference was found between the groups for the number of grafts used and the duration of aortic cross-clamping and cardiopulmonary bypass. No significant intergroup difference was seen for the mean diameter of the ascending aorta (p > 0.05). Annual changes in the aortic diameter were found to be extremely significantly different in both groups (p = 0.0001). Mean values of the aortic diameter at the level of the sinotubular junction and tubular ascending aorta, mean aortic diameters (p = 0.002 and p = 0.0001, respectively), annual increase in diameter (p = 0.0001 and p = 0.0001, respectively), and mean annual difference in diameter (p = 0.0001 and p = 0.0001, respectively) at one and three years postoperatively were statistically significantly different between the groups. Conclusion: In patients with ascending aortic dilatation who did not require surgical intervention and who had proximal anastomosis of the ascending aorta and underwent only CABG, we detected statistically significant increases in the diameter of the sinotubular junction and tubular aorta up to three years postoperatively. PMID:27701487

Anatomic Distribution of Fluorodeoxyglucose-Avid Para-aortic Lymph Nodes in Patients With Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takiar, Vinita; Fontanilla, Hiral P.; Eifel, Patricia J.

Purpose: Conformal treatment of para-aortic lymph nodes (PAN) in cervical cancer allows dose escalation and reduces normal tissue toxicity. Currently, data documenting the precise location of involved PAN are lacking. We define the spatial distribution of this high-risk nodal volume by analyzing fluorodeoxyglucose (FDG)-avid lymph nodes (LNs) on positron emission tomography/computed tomography (PET/CT) scans in patients with cervical cancer. Methods and Materials: We identified 72 PANs on pretreatment PET/CT of 30 patients with newly diagnosed stage IB-IVA cervical cancer treated with definitive chemoradiation. LNs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). Distances from the LNmore » center to the closest vessel and adjacent vertebral body were calculated. Using deformable image registration, nodes were mapped to a template computed tomogram to provide a visual impression of nodal frequencies and anatomic distribution. Results: We identified 72 PET-positive para-aortic lymph nodes (37 LPA, 32 AC, 3 RPC). All RPC lymph nodes were in the inferior third of the para-aortic region. The mean distance from aorta for all lymph nodes was 8.3 mm (range, 3-17 mm), and from the inferior vena cava was 5.6 mm (range, 2-10 mm). Of the 72 lymph nodes, 60% were in the inferior third, 36% were in the middle third, and 4% were in the upper third of the para-aortic region. In all, 29 of 30 patients also had FDG-avid pelvic lymph nodes. Conclusions: A total of 96% of PET positive nodes were adjacent to the aorta; PET positive nodes to the right of the IVC were rare and were all located distally, within 3 cm of the aortic bifurcation. Our findings suggest that circumferential margins around the vessels do not accurately define the nodal region at risk. Instead, the anatomical extent of the nodal basin should be contoured on each axial image to provide optimal coverage of the para-aortic nodal compartment.« less

Numerical assessment and comparison of pulse wave velocity methods aiming at measuring aortic stiffness.

PubMed

Obeid, Hasan; Soulat, Gilles; Mousseaux, Elie; Laurent, Stéphane; Stergiopulos, Nikos; Boutouyrie, Pierre; Segers, Patrick

2017-10-31

Pulse waveform analyses have become established components of cardiovascular research. Recently several methods have been proposed as tools to measure aortic pulse wave velocity (aPWV). The carotid-femoral pulse wave velocity (cf-PWV), the current clinical gold standard method for the noninvasive assessment of aPWV, uses the carotid-to-femoral pulse transit time difference (cf-PTT) and an estimated path length to derive cf-PWV. The heart-ankle PWV (ha-PWV), brachial-ankle PWV (ba-PWV) and finger-toe (ft-PWV) are also methods presuming to approximate aPWV based on time delays between physiological cardiovascular signals at two locations (~heart-ankle PTT, ha-PTT; ~brachial-ankle PTT, ba-PTT; ~finger-toe PTT, ft-PTT) and a path length typically derived from the subject's height. To test the validity of these methods, we used a detailed 1D arterial network model (143 arterial segments) including the foot and hand circulation. The arterial tree dimensions and properties were taken from the literature and completed with data from patient scans. We calculated PTTs with all the methods mentioned above. The calculated PTTs were compared with the aortic PTT (aPTT), which is considered as the absolute reference method in this study. The correlation between methods and aPTT was good and significant, cf-PTT (R 2   =  0.97; P  <  0.001; mean difference 5  ±  2 ms), ha-PTT (R 2   =  0.96; P  <  0.001; 150  ±  23 ms), ba-PTT (R 2   =  0.96; P  <  0.001; 70  ±  13 ms) and ft-PTT (R 2   =  0.95; P  <  0.001; 14  ±  10 ms). Consequently, good correlation was also observed for the PWV values derived with the tested methods, but absolute values differed because of the different path lengths used. In conclusion, our computer model-based analyses demonstrate that for PWV methods based on peripheral signals, pulse transit time differences closely correlate with the aortic transit time, supporting the use of these methods in clinical practice.

Vascular complications following intra-aortic balloon pump implantation: an updated review

PubMed Central

de Jong, Monique M; Lorusso, Roberto; Al Awami, Fatima; Matteuci, Francesco; Parise, Orlando; Lozekoot, Pieter; Bonacchi, Massimo; Maessen, Jos G; Johnson, Daniel M; Gelsomino, Sandro

2017-01-01

Background: The use of the intra-aortic balloon pump (IABP) as a support device remains controversial due to the fact that a number of studies have shown no benefit in end mortality whilst using this device. One of the reasons for this could be the increase in vascular complications when using the pump. Therefore, the aim of the present review was to assess the current literature available with regards to IABP vascular complications during the clinical situation. Methods: A literature search was performed, searching for IABP complications in adult human studies between 1990 and 2016. Results: A total of 20 reports were identified as fitting the criteria of this study. The majority of vascular complications were limb ischemia, bleeding or mesenteric ischemia. The overall incidence of vascular complications ranged from 0.94% to 31.1%. Diabetes, peripheral vascular disease and hypertension, as well as smoking were all identified as risk factors for complications following IABP. Furthermore, studies supported the use of sheathless balloon insertion to reduce the risk of complications. Conclusion: Major vascular complications, including limb and mesenteric ischemia as well as bleeding and hemorrhage, have been associated with IABP. However, the incidence of these complications was generally low. Further studies are still required to truly understand the risk/benefit associated with the use of IABP. PMID:28816093

Disruption of the Aortic Elastic Lamina and Medial Calcification Share Genetic Determinants in Mice

PubMed Central

Wang, Susanna S.; Martin, Lisa J.; Schadt, Eric E.; Meng, Haijin; Wang, Xuping; Zhao, Wei; Ingram-Drake, Leslie; Nebohacova, Martina; Mehrabian, Margarete; Drake, Thomas A.; Lusis, Aldons J.

2010-01-01

Background Disruption of the elastic lamina, as an early indicator of aneurysm formation, and vascular calcification frequently occur together in atherosclerotic lesions of humans. Methods and Results We now report evidence of shared genetic basis for disruption of the elastic lamina (medial disruption) and medial calcification in an F2 mouse intercross between C57BL/6J and C3H/HeJ on a hyperlipidemic apolipoprotein E (ApoE−/−) null background. We identified 3 quantitative trait loci (QTLs) on chromosomes 6, 13, and 18, which are common to both traits, and 2 additional QTLs for medial calcification on chromosomes 3 and 7. Medial disruption, including severe disruptions leading to aneurysm formation, and medial calcification were highly correlated and occurred concomitantly in the cross. The chromosome 18 locus showed a striking male sex-specificity for both traits. To identify candidate genes, we integrated data from microarray analysis, genetic segregation, and clinical traits. The chromosome 7 locus contains the Abcc6 gene, known to mediate myocardial calcification. Using transgenic complementation, we show that Abcc6 also contributes to aortic medial calcification. Conclusions Our data indicate that calcification, though possibly contributory, does not always lead to medial disruption and that in addition to aneurysm formation, medial disruption may be the precursor to calcification. PMID:20031637

The Effect of Aortic Compliance on Left Ventricular Power Requirement

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2009-11-01

Aortic compliance depends on both geometry and mechanical properties of the aorta. Reduction in arterial compliance has been associated with aging, smoking, and multiple cardiovascular diseases. Increased stiffness of the aorta affects the wave dynamics in the aorta by increasing both pulse pressure amplitude and wave speed. We hypothesized that decreased aortic compliance leads to an increased left ventricular power requirement for a fixed cardiac output due to altered pulse pressure and pulse wave velocity. We used a computational approach using the finite element method for solid and fluid domains coupled to each other by using the direct coupling method. A nonlinear material model was used for the solid wall. The fluid flow model was considered to be Newtonian, incompressible, and laminar. The simulation was performed for a heart rate of 75 beats per minute for six different compliances while keeping the cardiac output and the peripheral resistance constant. The results show a trend towards increased left ventricular energy expenditure per cycle with decreased compliance. The relevance of these findings to clinical observations will be discussed.

Alcohol consumption and mortality from aortic disease among Japanese men: The Japan Collaborative Cohort study.

PubMed

Shirakawa, Toru; Yamagishi, Kazumasa; Yatsuya, Hiroshi; Tanabe, Naohito; Tamakoshi, Akiko; Iso, Hiroyasu

2017-11-01

Only a few population-based prospective studies have examined the association between alcohol consumption and abdominal aortic aneurysm, and the results are inconsistent. Moreover, no evidence exists for aortic dissection. We examined the effect of alcohol consumption on risk of mortality from aortic diseases. A total of 34,720 men from the Japan Collaborative Cohort study, aged 40-79 years, without history of cardiovascular disease and cancer at baseline 1988 and 1990 were followed up until the end of 2009 for their mortality and its underlying cause. Hazard ratios of mortality from aortic diseases were estimated according to alcohol consumption categories of never-drinkers, ex-drinkers, regular drinkers of ≤30 g, and >30 g ethanol per day. During the median 17.9-year follow-up period, 45 men died of aortic dissection and 41 men died of abdominal aortic aneurysm. Light to moderate drinkers of ≤30 g ethanol per day had lower risk of mortality from total aortic disease and aortic dissection compared to never-drinkers. The respective multivariable hazard ratios (95% confidence intervals) were 0.46 (0.28-0.76) for total aortic disease and 0.16 (0.05-0.50) for aortic dissection. Heavy drinkers of >30 g ethanol per day did not have reduced risk of mortality from total aortic disease, albeit had risk variation between aortic dissection and abdominal aortic aneurysm. Light to moderate alcohol consumption was associated with reduced mortality from aortic disease among Japanese men. Copyright © 2017. Published by Elsevier B.V.

Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus formation.

PubMed

Giroux, Sylvie K; Labinaz, Marino X; Grisoli, Dominique; Klug, Andrew P; Veinot, John P; Burwash, Ian G

2010-01-01

Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. Pannus formation usually restricts systolic excursion of the occluding disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus formation. We describe an unusual case of intermittent, noncyclic dysfunction of a mechanical aortic prosthesis due to pannus formation in the absence of systolic restriction of disk excursion that presented with intermittent massive aortic regurgitation, severe ischemia, and shock. Pannus formation should be considered as a potential cause of acute intermittent severe aortic regurgitation in a patient with a mechanical aortic prosthesis.

Snare-assisted anterograde balloon mitral and aortic valvotomy using Inoue balloon catheter.

PubMed

Krishnan, Mangalath N; Syamkumar, M D; Sajeev, C G; Venugopal, K; Johnson, Francis; Vinaykumar, D; Velayudhan, C C; Jayakumar, T G

2007-01-02

We performed concurrent antegrade mitral and aortic valvotomy using Inoue dilatation catheter in 3 cases of combined rheumatic mitral and aortic stenosis. Following mitral valvotomy by standard procedure, aortic valve was crossed with the help of a floatation catheter. Stiff long length guide wire was fixed in descending aorta using a snare. Inoue catheter was threaded over the wire across the aortic valve and aortic valvotomy completed. Mitral valve area increased from mean 1 cm2 to 2 cm2; aortic gradient dropped from mean of 97 mm to 36 mm. Concurrent anterograde balloon mitral and aortic valvotomy may be effective and safe.

Correction of aortic insufficiency with an external adjustable prosthetic aortic ring.

PubMed

Gogbashian, Andrew; Ghanta, Ravi K; Umakanthan, Ramanan; Rangaraj, Aravind T; Laurence, Rita G; Fox, John A; Cohn, Lawrence H; Chen, Frederick Y

2007-09-01

Less invasive, valve-sparing options are needed for patients with aortic insufficiency (AI). We sought to evaluate the feasibility of reducing AI with an external adjustable aortic ring in an ovine model. To create AI, five sheep underwent patch plasty enlargement of the aortic annulus and root by placement of a 10 x 15 mm pericardial patch between the right and noncoronary cusps. An adjustable external ring composed of a nylon band was fabricated and placed around the aortic root. Aortic flow, aortic pressure, and left ventricular pressures were measured with the ring loose (off) and tightened (on). Mean regurgitant orifice area decreased by 86%, from 0.07 +/- 0.03 cm2 (ring loose, off) to 0.01 +/- 0.00 cm2 (ring tightened, on) [p < 0.01]. The regurgitant fraction decreased from 18 +/- 4% to 2 +/- 1% [p < 0.01]. The ring did not significantly affect stroke volume and aortic pressure. An ovine model of aortic root dilatation resulting in acute AI has been developed. In this model, application of an external, adjustable constricting aortic ring eliminated AI. An aortic ring may be a useful adjunct in reducing AI secondary to annular dilatation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Midulla, Marco, E-mail: marco.midulla@chru-lille.fr; Moreno, Ramiro, E-mail: ramoroa@gmail.com; Negre-Salvayre, Anne, E-mail: anne.negre-salvayre@inserm.fr

PurposeAlthough the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implicationsMethodsCT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were comparedmore » for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described.ResultsSegmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0–3) in 11 (78 %).ConclusionModeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.« less

Lipid Interventions in Aortic Valvular Disease.

PubMed

Choi, Kwang Jin; Tsomidou, Christiana; Lerakis, Stamatios; Madanieh, Raef; Vittorio, Timothy J; Kosmas, Constantine E

2015-10-01

Aortic valve stenosis is the most common valvular disease in the elderly population. Presently, there is increasing evidence that aortic stenosis (AS) is an active process of lipid deposition, inflammation, fibrosis and calcium deposition. The pathogenesis of AS shares many similarities to that of atherosclerosis; therefore, it was hypothesized that certain lipid interventions could prevent or slow the progression of aortic valve stenosis. Despite the early enthusiasm that statins may slow the progression of AS, recent large clinical trials did not consistently demonstrate a decrease in the progression of AS. However, some researchers believe that statins may have a benefit early on in the disease process, where inflammation (and not calcification) is the predominant process, in contrast to severe or advanced AS, where calcification (and not inflammation) predominates. Positron emission tomography using 18F-fluorodeoxyglucose and 18F-sodium fluoride can demonstrate the relative contributions of valvular calcification and inflammation in AS, and thus this method might potentially be useful in providing the answer as to whether lipid interventions at the earlier stages of AS would be more effective in slowing the progression of the disease. Currently, there is a strong interest in recombinant apolipoprotein A-1 Milano and in the development of new pharmacological agents, targeting reduction of lipoprotein (a) levels and possibly reduction of the expression of lipoprotein-associated phospholipase A2, as potential means to slow the progression of aortic valvular stenosis.

Survival after aortic valve replacement for severe aortic stenosis with low transvalvular gradients and severe left ventricular dysfunction

NASA Technical Reports Server (NTRS)

Pereira, Jeremy J.; Lauer, Michael S.; Bashir, Mohammad; Afridi, Imran; Blackstone, Eugene H.; Stewart, William J.; McCarthy, Patrick M.; Thomas, James D.; Asher, Craig R.

2002-01-01

OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.

Aortic Wall Extracellular Matrix Proteins Correlate with Syntax Score in Patients Undergoing Coronary Artery Bypass Surgery

PubMed Central

Chiong, Terri; Cheow, Esther S. H.; Woo, Chin C.; Lin, Xiao Y.; Khin, Lay W.; Lee, Chuen N.; Hartman, Mikael; Sze, Siu K.; Sorokin, Vitaly A.

2016-01-01

Aims: The SYNTAX score correlate with major cardiovascular events post-revascularization, although the histopathological basis is unclear. We aim to evaluate the association between syntax score and extracellular matrix histological characteristics of aortic punch tissue obtained during coronary artery bypass surgery (CABG). This analysis compares coronary artery bypass surgery patients with High and Low syntax score which were followed up for one year period. Methods and Results: Patients with High (score ≥ 33, (n=77)) and Low Syntax Scores (score ≤ 22, (n=71)) undergoing elective CABG were recruited prospectively. Baseline clinical characteristics and surgical risks were well matched. At 1 year, EMACCE (Sum of cardiovascular death, stroke, congestive cardiac failure, and limb, gut and myocardial ischemia) was significantly elevated in the High syntax group (P=0.022). Mass spectrometry (MS)-based quantitative iTRAQ proteomic results validated on independent cohort by immunohistochemistry (IHC) revealed that the High syntax group had significantly upraised Collagen I (P<0.0001) and Elastin (P<0.0001) content in ascending aortic wall. Conclusion: This study shows that aortic extracellular matrix (ECM) differ between High and Low syntax groups with up-regulation of Collagen I and Elastin level in High Syntax Score group. This identifies aortic punches collected during CABG as another biomarker source related with atherosclerosis severity and possible clinical outcome. PMID:27347220

Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.

PubMed

Osnabrugge, Ruben L J; Head, Stuart J; Genders, Tessa S S; Van Mieghem, Nicolas M; De Jaegere, Peter P T; van der Boon, Robert M A; Kerkvliet, J Marco; Kalesan, Bindu; Bogers, Ad J J C; Kappetein, A Pieter; Hunink, M G Myriam

2012-12-01

Transcatheter aortic valve replacement (TAVR) offers a new treatment option for patients with aortic stenosis, but costs may play a decisive role in decision making. Current studies are evaluating TAVR in an intermediate-risk population. We assessed the in-hospital and 1-year follow-up costs of patients undergoing TAVR and surgical aortic valve replacement (SAVR) at intermediate operative risk and identified important cost components. We prospectively collected clinical data on 141 patients undergoing TAVR and 405 undergoing SAVR. Propensity score matching yielded 42 matched pairs at intermediate risk. Costs were assessed using a detailed resource-use approach and compared using bootstrap methods. In-hospital costs were higher in TAVR patients than in SAVR patients (€40802 vs €33354, respectively; p=0.010). The total costs at 1 year were €46217 vs €35511, respectively (p=0.009). The TAVR was less costly with regard to blood products, operating room use, and length-of-stay. For intermediate-risk patients with severe aortic stenosis the costs at 1 year are higher for TAVR than for SAVR. The difference was mainly caused by the higher costs of the transcatheter valve and was not compensated by the lower costs for blood products and hospital stay in TAVR patients. Therefore, SAVR remains a clinically and economically attractive treatment option. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients

PubMed Central

Koutroumbas, Georgios; Georgianos, Panagiotis I.; Sarafidis, Pantelis A.; Protogerou, Athanase; Karpetas, Antonios; Vakianis, Pantelis; Raptis, Vassilios; Liakopoulos, Vassilios; Panagoutsos, Stylianos; Syrganis, Christos; Passadakis, Ploumis

2015-01-01

Background Increased arterial stiffness and aortic blood pressure (BP) are independent predictors of cardiovascular outcomes in end-stage renal disease. The 3-day interdialytic interval is associated with elevated risk of cardiovascular morbidity and mortality in haemodialysis. This study investigated differences in ambulatory aortic BP and arterial stiffness between the second and third day of the long interdialytic interval. Methods Ambulatory BP monitoring with Mobil-O-Graph monitor (IEM, Stolberg, Germany) was performed in 55 haemodialysis patients during a 3-day interval. Mobil-O-Graph records oscillometric brachial BP and pulse waves and calculates aortic BP and augmentation index (AIx) as measure of wave reflections, and pulse wave velocity (PWV) as measure of arterial stiffness. Results Ambulatory aortic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher during the third versus second interdialytic day (123.6 ± 17.0 versus 118.5 ± 17.1 mmHg, P < 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P < 0.001, respectively). Similar differences were noted for brachial BP. Ambulatory AIx and PWV were also significantly increased during the third versus second day (30.5 ± 9.9 versus 28.8 ± 9.9%, P < 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P < 0.001, respectively). Differences between Days 2 and 3 remained significant when day-time and night-time periods were compared separately. Aortic SBP and DBP, AIx and PWV showed gradual increases from the end of dialysis session onwards. Interdialytic weight gain was a strong determinant of the increase in the above parameters. Conclusions This study showed significantly higher ambulatory aortic BP, AIx and PWV levels during the third compared with the second interdialytic day. These findings support a novel pathway for increased cardiovascular risk during the third interdialytic day in haemodialysis. PMID:25920919

Aortic-Brachial Pulse Wave Velocity Ratio: A Measure of Arterial Stiffness Gradient Not Affected by Mean Arterial Pressure.

PubMed

Fortier, Catherine; Desjardins, Marie-Pier; Agharazii, Mohsen

2018-03-01

Aortic stiffness, measured by carotid-femoral pulse wave velocity (cf-PWV), is used for the prediction of cardiovascular risk. This mini-review describes the nonlinear relationship between cf-PWV and operational blood pressure, presents the proposed methods to adjust for this relationship, and discusses a potential place for aortic-brachial PWV ratio (a measure of arterial stiffness gradient) as a blood pressure-independent measure of vascular aging. PWV is inherently dependent on the operational blood pressure. In cross-sectional studies, PWV adjustment for mean arterial pressure (MAP) is preferred, but still remains a nonoptimal approach, as the relationship between PWV and blood pressure is nonlinear and varies considerably among individuals due to heterogeneity in genetic background, vascular tone, and vascular remodeling. Extrapolations from the blood pressure-independent stiffness parameter β (β 0 ) have led to the creation of stiffness index β, which can be used for local stiffness. A similar approach has been used for cardio-ankle PWV to generate a blood pressure-independent cardio-ankle vascular index (CAVI). It was recently demonstrated that stiffness index β and CAVI remain slightly blood pressure-dependent, and a more appropriate formula has been proposed to make the proper adjustments. On the other hand, the negative impact of aortic stiffness on clinical outcomes is thought to be mediated through attenuation or reversal of the arterial stiffness gradient, which can also be influenced by a reduction in peripheral medium-sized muscular arteries in conditions that predispose to accelerate vascular aging. Arterial stiffness gradient, assessed by aortic-brachial PWV ratio, is emerging to be at least as good as cf-PWV for risk prediction, but has the advantage of not being affected by operating MAP. The negative impacts of aortic stiffness on clinical outcomes are proposed to be mediated through attenuation or reversal of arterial stiffness gradient. Aortic-brachial PWV ratio, a measure of arterial stiffness gradient, is independent of MAP.

Endovascular treatment of traumatic thoracic aortic injuries: short- and medium-term Follow-up.

PubMed

Fernandez, Valentín; Mestres, Gaspar; Maeso, Jordi; Domínguez, José Manuel; Aloy, M Carmen; Matas, Manel

2010-02-01

Successful thoracic endovascular aortic repair (TEVAR) with low rates of complications has been referred to in the treatment of traumatic thoracic aortic injuries; however, we still do not know the long-term behavior. In this series, short- and intermediate-term results of TEVAR of traumatic aortic injuries are analyzed. The clinical charts and courses of 20 patients (mean age, 31.8 years; age range, 15-65 years; 14 [70%] men) with traumatic thoracic aortic injuries treated with TEVAR were retrospectively reviewed. Mean delay from trauma to intervention was 15 days (range, 0-180 days). The initial success rate was 100%, with no deaths or intraoperative leaks, although in 4 (20%) patients, injuries were repaired in the arterial access site. The mean postoperative follow-up was 43.53 months (range, 5.5-108.0 months). Four (20%) patients required reintervention: 2 postoperative revascularizations of the left subclavian artery (20% of the patients in whom the ostium was intentionally occluded) and 2 aortic reinterventions (endovascular treatment of a collapsed stent graft and open repair after thrombosis of another stent graft). All reinterventions were successfully performed and no additional complications were registered during follow-up. Asymptomatic findings related to the stent graft included lack of proximal device-wall apposition in 8 patients (40%), intragraft mural thrombus formation during the first 6 months in 7 patients (35%), and an asymptomatic fracture of the longitudinal reinforcing bar of the stent graft 4 years later in 1 patient (5%). Although not completely exempt of complications, TEVAR provides a reliable method for the treatment of traumatic thoracic aortic injuries with good results in the short- and medium-term follow-up. All complications have been treated successfully. Long-term evolution of lack of proximal device-wall apposition and intragraft mural thrombus formation should be closely monitored to prevent long-term complications. Copyright 2006 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Maximum Diameter Measurements of Aortic Aneurysms on Axial CT Images After Endovascular Aneurysm Repair: Sufficient for Follow-up?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumueller, Stephan, E-mail: Stephan.Baumueller@usz.ch; Nguyen, Thi Dan Linh, E-mail: ThiDanLinh.Nguyen@usz.ch; Goetti, Robert Paul, E-mail: RobertPaul.Goetti@usz.ch

2011-12-15

Purpose: To assess the accuracy of maximum diameter measurements of aortic aneurysms after endovascular aneurysm repair (EVAR) on axial computed tomographic (CT) images in comparison to maximum diameter measurements perpendicular to the intravascular centerline for follow-up by using three-dimensional (3D) volume measurements as the reference standard. Materials and Methods: Forty-nine consecutive patients (73 {+-} 7.5 years, range 51-88 years), who underwent EVAR of an infrarenal aortic aneurysm were retrospectively included. Two blinded readers twice independently measured the maximum aneurysm diameter on axial CT images performed at discharge, and at 1 and 2 years after intervention. The maximum diameter perpendicular tomore » the centerline was automatically measured. Volumes of the aortic aneurysms were calculated by dedicated semiautomated 3D segmentation software (3surgery, 3mensio, the Netherlands). Changes in diameter of 0.5 cm and in volume of 10% were considered clinically significant. Intra- and interobserver agreements were calculated by intraclass correlations (ICC) in a random effects analysis of variance. The two unidimensional measurement methods were correlated to the reference standard. Results: Intra- and interobserver agreements for maximum aneurysm diameter measurements were excellent (ICC = 0.98 and ICC = 0.96, respectively). There was an excellent correlation between maximum aneurysm diameters measured on axial CT images and 3D volume measurements (r = 0.93, P < 0.001) as well as between maximum diameter measurements perpendicular to the centerline and 3D volume measurements (r = 0.93, P < 0.001). Conclusion: Measurements of maximum aneurysm diameters on axial CT images are an accurate, reliable, and robust method for follow-up after EVAR and can be used in daily routine.« less

One-stage hybrid surgery for acute Stanford type A aortic dissection with David operation, aortic arch debranching, and endovascular graft: a case report

PubMed Central

Liu, Lulu; Qin, Chaoyi; Hou, Jianglong; Zhu, Da; Zhang, Bengui; Ma, Hao

2016-01-01

Acute Stanford type A aortic dissection requires an extremely complex surgical strategy and presents high risk of complications. Although many different procedures were reported to treat this aortic dissection, high mortality rate and incidences of complications still exist. This study presents a 59-year-old lady with acute Stanford type A aortic dissection, which originated from the aortic root to proximal part of right external iliac artery and involved the brachiocephalic trunk, left carotid artery, celiac trunk, and left renal artery. The patient underwent one-stage hybrid surgery of David procedures, debranching, and endovascular aortic repair under ultrasound-guided aortic arch cannulation cardiopulmonary bypass (CPB). The surgery was successfully performed, and the patient showed no post-operative complication. The one-staged hybrid surgery of David procedures, debranching, and endovascular aortic repair provides novel and well-designed combined techniques for treating complex acute Stanford type A aortic dissection. Our techniques significantly lowered the risks, thereby expanding the indications of surgical intervention for acute Stanford type A aortic dissection. PMID:28149590

[Progress and challenge of Stanford type A aortic dissection in China].

PubMed

Sun, L Z; Li, J R

2017-04-01

In recent 20 years, the rapid development of acute Stanford type A aortic dissection in China has been mainly due to three aspects: (1) the refined classification of aortic dissection based on Stanford classification, (2) right axillary artery canal and selective cerebral perfusion technology become basic cardiopulmonary bypass strategy for Stanford type A aortic dissection, and (3) total aortic arch replacement and descending aortic stent graft surgery (Sun's surgery) become the standard treatment of Stanford type A aortic dissection. However, there are still many problems in the diagnosis and treatment of aortic dissection in China, such as: (1) unstandardized, lack of comprehensive guidelines of aortic dissection, (2) immature, perioperative organ protection and intraoperative blood protection technology remains a big flaw, and (3) it takes a long time to get patient prepared for surgery. In conclusion, as to the issue of the management of acute Stanford type A aortic dissection, there will be a long way for Chinese doctors to go. Peers should pay more attention to this problem and take more efforts, so that the outcome of acute Stanford type A aortic dissection surgical patients can be improved.

One-stage hybrid surgery for acute Stanford type A aortic dissection with David operation, aortic arch debranching, and endovascular graft: a case report.

PubMed

Liu, Lulu; Qin, Chaoyi; Hou, Jianglong; Zhu, Da; Zhang, Bengui; Ma, Hao; Guo, Yingqiang

2016-12-01

Acute Stanford type A aortic dissection requires an extremely complex surgical strategy and presents high risk of complications. Although many different procedures were reported to treat this aortic dissection, high mortality rate and incidences of complications still exist. This study presents a 59-year-old lady with acute Stanford type A aortic dissection, which originated from the aortic root to proximal part of right external iliac artery and involved the brachiocephalic trunk, left carotid artery, celiac trunk, and left renal artery. The patient underwent one-stage hybrid surgery of David procedures, debranching, and endovascular aortic repair under ultrasound-guided aortic arch cannulation cardiopulmonary bypass (CPB). The surgery was successfully performed, and the patient showed no post-operative complication. The one-staged hybrid surgery of David procedures, debranching, and endovascular aortic repair provides novel and well-designed combined techniques for treating complex acute Stanford type A aortic dissection. Our techniques significantly lowered the risks, thereby expanding the indications of surgical intervention for acute Stanford type A aortic dissection.

Subacute Staphylococcus epidermidis Bacterial Endocarditis Complicated by Mitral-Aortic Intervalvular Fibrosa Pseudoaneurysm

DTIC Science & Technology

2012-12-01

Staphylococcus epidermidis Bacterial Endocarditis Complicated byMitral-Aortic Intervalvular Fibrosa Pseudoaneurysm Diane Elegino-Steffens,1 Amy Stratton,1... endocarditis . 1. Introduction The mitral-aortic intervalvular fibrosa (MAIF), also known as the mitral-aortic membrane, is a fibrous region of the heart...of his aortic valve for severe aortic regurgitation that was subsequently found to have infective endocarditis prompting antibiotic treatment. His

Aortopathy in patients with bicuspid aortic valve stenosis: role of aortic root functional parameters.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Espinoza, Andres; Dubslaff, Georg; Fey, Beatrix; Theis, Bernhard; Petersen, Iver; Borger, Michael A; Kuntze, Thomas

2016-02-01

We prospectively examined functional characteristics of the aortic root and transvalvular haemodynamic flow in order to define factors associated with the severity of aortopathy in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. A total of 103 consecutive patients with BAV stenosis (mean age 61 ± 9 years, 66% male) underwent aortic valve replacement ± concomitant aortic surgery from January 2012 through March 2014. All patients underwent preoperative cardiac magnetic resonance imaging (MRI) in order to evaluate the systolic transvalvular flow and the following functional parameters: (i) angulation between the left ventricular outflow axis and the aortic root, (ii) geometrical orientation of residual aortic valve orifice and (iii) BAV cusp fusion pattern. MRI data were used to guide sampling of the ascending aorta during surgery [i.e. jet-sample from the area where the flow-jet impacts on the aortic wall and control sample from the opposite aortic wall (obtained from the aortotomy site)]. Aortopathy was quantified by means of a histological sum-score (0 to 21+) in each sample. A significant correlation was found between histological sum-score in the jet-sample and the angle between the LV outflow axis and the aortic root (r = 0.6, P = 0.007). Moreover, there was a linear correlation between proximal aortic diameter and the angle between systolic flow-jet and ascending aortic wall (r = 0.5, P = 0.006). Logistic regression identified the angle between the LV outflow axis and the aortic root (OR 1.1, P = 0.04) and the angle between the flow-jet and the aortic wall (OR 1.2, P = 0.001) as independent predictors of an indexed proximal aortic diameter ≥22 mm/m(2). Functional parameters of the aortic root may be used to predict the severity of aortopathy in patients with BAV stenosis, and may be useful in predicting future risk of aortic disease in such patients. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Total Endovascular Aortic Repair in a Patient with Marfan Syndrome.

PubMed

Amako, Mau; Spear, Rafaëlle; Clough, Rachel E; Hertault, Adrien; Azzaoui, Richard; Martin-Gonzalez, Teresa; Sobocinski, Jonathan; Haulon, Stéphan

2017-02-01

The aim of this study is to describe a total endovascular aortic repair with branched and fenestrated endografts in a young patient with Marfan syndrome and a chronic aortic dissection. Open surgery is the gold standard to treat aortic dissections in patients with aortic disease and Marfan syndrome. In 2000, a 38-year-old man with Marfan syndrome underwent open ascending aorta repair for an acute type A aortic dissection. One year later, a redo sternotomy was performed for aortic valve replacement. In 2013, the patient presented with endocarditis and pulmonary infection, which necessitated tracheostomy and temporary dialysis. In 2014, the first stage of the endovascular repair was performed using an inner branched endograft to exclude a 77-mm distal arch and descending thoracic aortic aneurysm. In 2015, a 63-mm thoracoabdominal aortic aneurysm was excluded by implantation of a 4-fenestrated endograft. Follow-up after both endovascular repairs was uneventful. Total aortic endovascular repair was successfully performed to treat a patient with arch and thoraco-abdominal aortic aneurysm associated with chronic aortic dissection and Marfan syndrome. The postoperative images confirmed patency of the endograft and its branches, and complete exclusion of the aortic false lumen. Endovascular repair is a treatment option in patients with connective tissue disease who are not candidates for open surgery. Long-term follow-up is required to confirm these favorable early outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.