Normal Aortic Valve Research Articles

Videographic conceptual dynamic representation of bicuspid aortic valve anatomic configurations and structural inter-relationships.

Videographic conceptual dynamic representation of bicuspid aortic valve anatomic configurations and structural inter-relationships.

Prevalence of Aortic Valve Stenosis in Patients With ST-Segment Elevation Myocardial Infarction and Effect on Long-Term Outcome

Several studies have shown an association between aortic valve stenosis (AS), atherosclerosis and cardiovascular risk factors. These risk factors are frequently encountered in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the prevalence and the prognostic implications of AS in patients presenting with STEMI. A total of 2041 patients (61 ± 12 years old, 76% male) admitted with STEMI and treated with primary percutaneous coronary intervention were included. Patients with previous myocardial infarction and previous aortic valve replacement were excluded. Echocardiography was performed at index admission. Patients were divided in 3 groups: 1) any grade of AS, 2) aortic valve sclerosis and 3) normal aortic valve. Any grade of AS was defined as an aortic valve area ≤2.0 cm2. The primary endpoint was all-cause mortality. The prevalence of AS was 2.7% in the total population and it increased with age (1%, 3%, 7% and 16%, in the patients aged <65 years, 65 to 74 years, 75 to 84 years and ≥85 years, respectively). Patients with AS showed a significantly higher mortality rate when compared to the other two groups (p < 0.001) and AS was independently associated with all-cause mortality, with a HR of 1.81 (CI 95%: 1.02 to 3.22; p=0.04). In conclusion, AS is not uncommon in patients with STEMI, and concomitant AS in patients with first STEMI is independently associated with all-cause mortality at long-term follow up.

LncRNA AFAP1-AS1 promotes M1 polarization of macrophages and osteogenic differentiation of valve interstitial cells.

Little is known about the biological functions and underlying mechanisms of long non-coding RNA AFAP1-AS1 in degenerative calcified aortic valve disease (DCAVD). This study aims to explore whether AFAP1-AS1 regulates macrophage polarization in aortic valve calcification. Macrophage polarization and AFAP1-AS1 expression were detected in normal and calcified aortic valves of DCAVD patients. To explore the effect of AFAP1-AS1 on macrophage polarization, gain and loss of function were performed in THP-1 cells, and the percentage of M1 and M2 and the expressions of M1 and M2 markers were analyzed. Meanwhile, osteogenic differentiation was examined in valve interstitial cells (VICs). Compared with normal valves, there were more M1, less M2, and high AFAP1-AS1 expressions in calcified aortic valves, which may indicate a relationship between AFAP1-AS1 and macrophage polarization. AFAP1-AS1 overexpression promoted M1 polarization in lipopolysaccharide (LPS) and interferon gamma (IFN-γ)-treated THP-1 cells but inhibited M2 polarization, as well as augmented VIC osteogenic differentiation. On the contrary, the silence of AFAP1-AS1 could induce macrophage to M2-type and inhibit VIC osteogenic differentiation. These results elucidate that AFAP1-AS1 can promote M1 macrophages polarization to aggravate VIC osteogenic differentiation, playing a role in aortic valve calcification.

Molecular and Mechanical Mechanisms of Calcification Pathology Induced by Bicuspid Aortic Valve Abnormalities.

Bicuspid aortic valve (BAV) is a congenital defect affecting 1–2% of the general population that is distinguished from the normal tricuspid aortic valve (TAV) by the existence of two, rather than three, functional leaflets (or cusps). BAV presents in different morphologic phenotypes based on the configuration of cusp fusion. The most common phenotypes are Type 1 (containing one raphe), where fusion between right coronary and left coronary cusps (BAV R/L) is the most common configuration followed by fusion between right coronary and non-coronary cusps (BAV R/NC). While anatomically different, BAV R/L and BAV R/NC configurations are both associated with abnormal hemodynamic and biomechanical environments. The natural history of BAV has shown that it is not necessarily the primary structural malformation that enforces the need for treatment in young adults, but the secondary onset of premature calcification in ~50% of BAV patients, that can lead to aortic stenosis. While an underlying genetic basis is a major pathogenic contributor of the structural malformation, recent studies have implemented computational models, cardiac imaging studies, and bench-top methods to reveal BAV-associated hemodynamic and biomechanical alterations that likely contribute to secondary complications. Contributions to the field, however, lack support for a direct link between the external valvular environment and calcific aortic valve disease in the setting of BAV R/L and R/NC BAV. Here we review the literature of BAV hemodynamics and biomechanics and discuss its previously proposed contribution to calcification. We also offer means to improve upon previous studies in order to further characterize BAV and its secondary complications.

Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis

BackgroundCalcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear.MethodsThe gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein–protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation.ResultsWe identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively.ConclusionsThis study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.

The normal aortic valve leaflets effective height in pediatric patients: A guide to aortic valve repair

Aortic valve (AV) repair is an attractive option in pediatric patients because it avoids the long-term risk of anticoagulation, allows growth, and postpones AV replacement. In the past decade, favorable results in the adult patients and the emergence of a systematic approach to the AV partly explain the 3-fold increase in pediatric AV repairs.1 The effective height (eH) is defined as the difference between the central free margins and the atrioventricular junction and is used as predictor of valve repair durability in adult patients.

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

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

Bicuspid Aortic Valve in Infants, Children, and Adolescents: A Review for Primary Care Providers.

1. Talha Niaz, MBBS* 2. Jonathan N. Johnson, MD*,† 3. Frank Cetta, MD*,† 4. Timothy M. Olson, MD*,† 5. Donald J. Hagler, MD*,† 1. *Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, and 2. †Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN * Abbreviations: AHA : : American Heart Association BAV : : bicuspid aortic valve TTE : : transthoracic echocardiography Bicuspid aortic valve is the most common congenital heart defect in children, adolescents, and adults. Primary care providers play an important role in screening, referral, and follow-up of these patients and should be aware of the family screening guidelines, sports participation recommendations, and periodic follow-up requirements for adequate surveillance of the complications that arise from bicuspid aortic valve. After reading this article, readers should be able to: 1. Describe the epidemiology and anatomy of bicuspid aortic valve (BAV). 2. Understand the clinical presentation and diagnosis of BAV in infants, children, and adolescents. 3. Identify the various complications of BAV disease. 4. Discuss the management and follow-up requirements for BAV. 5. Analyze the family screening and sports participation guidelines for patients with BAV. Bicuspid aortic valve (BAV) is the most common congenital heart defect in children, adolescents, and adults. (1) It is a heterogeneous disease that affects both the aortic valve and the aorta. It can lead to many complications, including aortic valve stenosis, regurgitation, or endocarditis. (2)(3) It also can lead to dilation of the aorta, predisposing individuals to a significantly higher risk of aortic aneurysm and dissection. (4) Although most individuals with BAV present with these long-term complications during adulthood, a considerable number of patients may also present during childhood and adolescence with early-onset disease; that may require interventions in up to 12% to 15% of the patients. (5)(6) Therefore, patients with BAV require lifelong follow-up and surveillance. BAV has multiple implications in terms of sports participation and family screening, making it an important subject for primary care providers. This article reviews the anatomy, genetics, presentation, diagnosis, …

Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.

Calcific aortic valve disease sits at the confluence of multiple world-wide epidemics of aging, obesity, diabetes, and renal dysfunction, and its prevalence is expected to nearly triple over the next 3 decades. This is of particularly dire clinical relevance, as calcific aortic valve disease can progress rapidly to aortic stenosis, heart failure, and eventually premature death. Unlike in atherosclerosis, and despite the heavy clinical toll, to date, no pharmacotherapy has proven effective to halt calcific aortic valve disease progression, with invasive and costly aortic valve replacement representing the only treatment option currently available. This substantial gap in care is largely because of our still-limited understanding of both normal aortic valve biology and the key regulatory mechanisms that drive disease initiation and progression. Drug discovery is further hampered by the inherent intricacy of the valvular microenvironment: a unique anatomic structure, a complex mixture of dynamic biomechanical forces, and diverse and multipotent cell populations collectively contributing to this currently intractable problem. One promising and rapidly evolving tactic is the application of multiomics approaches to fully define disease pathogenesis. Herein, we summarize the application of (epi)genomics, transcriptomics, proteomics, and metabolomics to the study of valvular heart disease. We also discuss recent forays toward the omics-based characterization of valvular (patho)biology at single-cell resolution; these efforts promise to shed new light on cellular heterogeneity in healthy and diseased valvular tissues and represent the potential to efficaciously target and treat key cell subpopulations. Last, we discuss systems biology- and network medicine-based strategies to extract meaning, mechanisms, and prioritized drug targets from multiomics datasets.

Feasibility of two-dimensional speckle-tracking echocardiography of aortic valve in patients with calcific aortic valve disease

Calcific aortic valve (AV) disease is associated with increased stiffness and reduced motion of AV leaflets, has a progressive course, and can develop into aortic stenosis (AS). Our aim was to evaluate whether two-dimensional speckle-tracking echocardiography (STE) may be used for the assessment of AV stiffness. We applied STE to AV leaflets in patients with various degrees of degenerative changes of AV and measured strain as an absolute value of the radial deformation of AV leaflets. Deformation of AV expressed as averaged AV strain was greatest in patients with a normal AV (23.4 ± 6.4%), compared to those with aortic sclerosis (12.9 ± 3.2%), moderate-to-severe AS (11.9 ± 4%), and severe AS (10.9 ± 3.5%) (p < 0.01). A non-linear relationship and moderate correlation of AV strain with transvalvular hemodynamic parameters was observed. In patients with mild-to-moderate AS, the strain of AV leaflets also correlated negatively with AV calcification (r = −0.59, p = 0.008). Good inter-observer agreement was obtained for averaged AV strain with a coefficient of variation of 0.15 and an interclass correlation coefficient of 0.94 (p < 0.0001). In this study we demonstrated that deformation of AV leaflets as assessed by STE might be a potential method for a non-invasive evaluation of AV biomechanical properties and of the progression of calcific aortic disease. Further development of the two-dimensional speckle tracking technique specifically for valve structures is needed to enable a better quantification of leaflet deformation.

Warfarin Induces Calcification of the Aortic Valve Through Extracellular Signal-regulated Kinase 1/2 and β-catenin Signaling

BackgroundRecent clinical evidence suggests an association between warfarin use and calcification of the aortic valve. We sought to determine the effect of warfarin on aortic valve interstitial cell (AVIC) osteogenic protein expression and the signaling pathways by which this effect is mediated. MethodsHuman AVICs were isolated from normal aortic valves of patients undergoing cardiac transplantation, whereas diseased AVICs were isolated from patients undergoing aortic valve replacement for aortic stenosis. AVICs were treated with various anticoagulants, and osteogenic protein expression was evaluated using immunoblotting. Phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and extracellular signal-regulated kinase 1/2 (ERK1/2) was evaluated after treatment with warfarin. AVICs were pretreated with LRP6 inhibitor dkk1 and ERK1/2 inhibitor PD98059 followed by treatment with warfarin, and osteogenic protein expression was evaluated. ResultsWarfarin, but not heparin or dabigatran, significantly increased Runx-2 and Osx expression in both normal and diseased human AVICs. Upregulation of β-catenin protein expression and nuclear translocation occurred in diseased AVICs but not normal AVICs after warfarin treatment. Warfarin induced phosphorylation of LRP6 in diseased AVICs only and phosphorylation of ERK1/2 in both normal and diseased AVICs. LRP6 inhibition attenuated warfarin-induced Runx-2 expression in diseased AVICs. ERK1/2 inhibition attenuated warfarin-induced Runx-2 expression in both normal and diseased AVICs. ConclusionsWarfarin induces osteogenic activity in normal and diseased isolated human AVICs. This effect is mediated by ERK1/2 in both diseased and normal AVICs, but in diseased AVICs β-catenin signaling also plays a role. These results implicate the role of warfarin in aortic valve calcification and highlight potential mechanisms for warfarin-induced aortic stenosis.

3D Contractile Responses of Normal and Diseased Human Aortic Valve Interstitial Cells

Objective: The bicuspid aortic valve (BAV) contains two rather than the normal three leaflets; and is actually a spectrum of structural anomalies that can include a raphe region. For reasons that remain unclear, BAVs calcify faster than normal aortic valves (NAVs). Structural remodeling in BAV is driven by aortic valve interstitial cells (AVICs) that can become activated due to mechanical and biochemical cues. Increased contractility is a hallmark of activation and reflects AVIC biophysical state. In this study, we assessed the 3D contractile responses of AVICs extracted from BAVs and NAVs to develop an improved understanding of their intrinsic function and differences. Methods: AVICs from the raphe and non-raphe regions of human BAVs were assessed. AVICs from human NAVs served as controls. AVICs and fluorescent microbeads were seeded within PEG hydrogels. Image stacks of an AVIC and surrounding fluorescent microbeads were obtained within normal and relaxed (CytochalasinD) conditions. The positions of the beads were tracked between each image stack using a custom software which output local hydrogel displacements (Figure 1A-C). Results: AVICs from BAVs produced lower levels of hydrogel displacements than NAVs (Figure 1D). Interestingly, AVICs from the raphe and non-raphe regions produced similar levels of displacements. AVICs produced complex displacement fields with regions of contraction and expansion. Furthermore, contractile displacements occurred at cell pseudopods whereas expansive displacements occurred near the mid-section of the cell. Conclusions: Contractile behaviors differed substantially between BAVs and NAVs, which suggests that AVICs are intrinsically different between the two valve types. This result suggests that AVICs are fundamentally different and that the larger BAV disorder affects the cellular scale as well as the organ-level anatomy, and will lay basis for future cellular-based therapies.

Donor Bicuspid Aortic Valve: Double Trouble or No Problem?

<h3>Introduction</h3> Valvular disease in pediatric donor hearts may be a relative contraindication to graft use. Outcomes following use of donor hearts with milder forms of valvular disease have not been previously reported. We describe 4 cases of pediatric heart transplantation (HTx) in which the donor heart had a bicuspid aortic valve (BAV). <h3>Case Report</h3> Of the 469 HTx performed at our center since 1985, 4 donor hearts had a BAV. All recipients were female; median age 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow up. Two patients transferred to adult care and 2 patients are followed by our clinic. In follow up, no patient required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild to moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the bicuspid aortic valve. <h3>Summary</h3> On short- and intermediate-term follow up, donor hearts with bicuspid aortic valve demonstrated acceptable graft longevity and valvular function. A functionally normal bicuspid aortic valve in a pediatric heart transplant donor should not be a contraindication to organ acceptance.

Modeling of aortic valve stenosis using fluid-structure interaction method.

Fluid structure interaction (FSI) is defined as interaction of the structures with contacting fluids. The aortic valve experiences the interaction with blood flow in systolic phase. In this study, we have tried to predict the hemodynamics of blood flow through a normal and stenotic aortic valve in two relaxation and exercise conditions using a three-dimensional FSI method. The aorta valve was modeled as a three-dimensional geometry including a normal model and two others with 25% and 50% stenosis. The geometry of the aortic valve was extracted from CT images and the models were generated by MMIMCS software and then they were implemented in ANSYS software. The pulsatile flow rate was used for all cases and the numerical simulations were conducted based on a time-dependent domain. The obtained results including the velocity, pressure, and shear stress contours in different systolic time sequences were explained and discussed. The maximum blood flow velocity in relaxation phase was obtained 1.62 m/s (normal valve), 3.78 m/s (25% stenosed valve), and 4.73 m/s (50% stenosed valve). In exercise condition, the maximum velocities are 2.86, 4.32, and 5.42 m/s respectively. The maximum blood pressure in relaxation phase was calculated 111.45 mmHg (normal), 148.66 mmHg (25% stenosed), and 164.21 mmHg (50% stenosed). However, the calculated values in exercise situation were 129.57, 163.58, and 191.26 mmHg.The validation of the predicted results was also conducted using existing literature. We believe that such model are useful tools for biomechanical experts. The further studies should be done using experimental data and the data are implemented on the boundary conditions for better comparison of the results.

Influence of aneurysmal aortic root geometry on mechanical stress to the aortic valve leaflet.

While mechanical stress caused by blood flow, e.g. wall shear stress (WSS), and related parameters, e.g. oscillatory shear index (OSI), are increasingly being recognized as key moderators of various cardiovascular diseases, studies on valves have been limited because of a lack of appropriate imaging modalities. We investigated the influence of aortic root geometry on WSS and OSI on the aortic valve (AV) leaflet. We applied our novel approach of intraoperative epi-aortic echocardiogram to measure the haemodynamic parameters of WSS and OSI on the AV leaflet. Thirty-six patients were included, which included those who underwent valve-sparing aortic root replacement (VSARR) with no significant aortic regurgitation (n = 17) and coronary artery bypass graft (CABG) with normal AV (n = 19). At baseline, those who underwent VSARR had a higher systolic WSS (0.52 ± 0.12 vs. 0.32 ± 0.08 Pa, respectively, P < 0.001) and a higher OSI (0.37 ± 0.06 vs. 0.29 ± 0.04, respectively, P < 0.001) on the aortic side of the AV leaflet than those who underwent CABG. Multivariate regression analysis revealed that the size of the sinus of Valsalva had a significant association with WSS and OSI. Following VSARR, WSS and OSI values decreased significantly compared with the baseline values (WSS: 0.29 ± 0.12 Pa, P < 0.001; OSI: 0.26 ± 0.09, P < 0.001), and became comparable to the values in those who underwent CABG (WSS, P = 0.42; OSI, P = 0.15). Mechanical stress on the AV gets altered in correlation with the size of the aortic root. An aneurysmal aortic root may expose the leaflet to abnormal fluid dynamics. The VSARR procedure appeared to reduce these abnormalities.

Bicuspid aortic valve flow dynamics using blood speckle tracking in children

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Labatt Family Heart Centre Background Bicuspid aortic valves (BAV) are the most common form of congenital heart disease with a prevalence of up to 2%. Fusion of the aortic cusps result in complex flow patterns in the aortic root which may contribute to the risk of progressive dilation. Imaging these patterns with conventional echocardiography is challenging due to the angle dependency of colour Doppler. Blood speckle tracking (BST) is a novel method based on high-frame rate ultrasound that is less angle-independent and developed to evaluate complex flow. Purpose The aims of this study were to 1) describe and quantify flow patterns in the aortic root using blood speckle tracking and 2) quantitatively compare flow parameters (energy loss, vorticity, kinetic energy) between paediatric patients with BAVs and those with normal aortic valves. Methods Clinical and routine echocardiographic parameters were collected for children with normal and BAVs. Children were imaged using a commercially available clinical scanner with research software enabling the acquisition of high-frame rate imaging and blood speckle tracking. Aortic root energy loss, vorticity and kinetic energy were measured in the parasternal long axis view. Results Data from 46 patients were analyzed (31 normal aortic valves, 15 BAVs) with no significant difference in age, height, weight or BSA between groups. Nine patients (60%) had right-left fusion; 6 (40%) had right-non fusion. Qualitative flow assessment in aortic root demonstrated disturbed flow in the BAV group (see figure) generally directed towards the non-fused cusp (i.e non coronary cusp in right-left fusion). Patients with a BAV had higher aortic valve peak velocity (2.1 m/s vs 0.9 m/s, p&amp;lt; 0.001); aortic root systolic energy loss (4.29 mW/m vs 1.79 mW/m, p&amp;lt; 0. 001), vorticity (38.7 1/s vs 31.1 1/s, p&amp;lt; 0.01) and kinetic energy (34.5 mJ/m vs 24.5 mJ/m, p = 0.04) compared to those with normal aortic valves. Conclusion(s) Blood speckle tracking can demonstrate altered flow patterns in the aortic root in patients with BAV. These patients have increased energy losses, vorticity and kinetic energy when compared to age matched patients with normal aortic valves however the relationship of theses parameters to aortic root dilation remains to be demonstrated. Abstract Figure. Flow patterns (A-C) and analysis (D-F)

Prospective validation of a non-invasive method to estimate myocardial work in aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): ANR - Maestro project Background Stratification of aortic stenosis patients remains challenging and robust indices are required. Myocardial work assessment is a new afterload independent alternative to evaluate left ventricular function. Although, this method was developed in patients with normal aortic valve. We previously developed an integrated cardiovascular system simulated by a computational model to estimate non-invasively myocardial work in aortic stenosis patients* (figure 1A). In the present study, we tested our model in a prospective population of AS patients. Method and results 9 patients with severe AS (aortic valve area &amp;lt; 1cm2) were included. A complete trans-thoracic echocardiography with a non-invasive blood pressure by brachial artery cuff were realized immediately before a left heart catheterization to have an invasive left ventricular pressure. Myocardial work is then calculated with non-invasive and invasive LV pressure combined to LV strain curves. For constructive and wasted work, root mean squared between invasive and estimated measures were respectively r2 = 0.92 and r2 = 0.94 (figure 1B) Conclusion The proposed model is efficient to estimate non-invasively myocardial work indices in AS-patients. These afterload independent indices could permit in future to better stratify this population. *Owashi KP, Hubert A and al. Model-based estimation of left ventricular pressure and myocardial work in aortic stenosis. PlosOne 2020. Mar 3;15(3):e0229609 Abstract Figure 1

How common is aortic dilatation?

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

Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis

Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies. Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level. While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease. Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis. The study was done on valvular tissues 0–17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS. High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure. RNA-Seq was used to identify regulation of N-glycan related enzymes. The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis. In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures. In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group. Three sialylated N-glycans showed common elevation in AS independent of age. On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages. Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS. This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.

Systolic stretching of the ascending aorta.

IntroductionLongitudinal stretching of the aorta due to systolic heart motion contributes to the stress in the wall of the ascending aorta. The objective of this study was to assess longitudinal systolic stretching of the aorta and its correlation with the diameters of the ascending aorta and the aortic root.Material and methodsAortographies of 122 patients were analyzed. The longitudinal systolic stretching of the aorta caused by the contraction of the heart during systole and the maximum dimensions of the aortic root and ascending aorta were measured in all patients.ResultsThe maximum dimension of the aortic root was on average 34.9 ±4.5 mm and the mean diameter of the ascending aorta was 33.9 ±5.4 mm. The systolic aortic stretching negatively correlated with age (r = –0.49, p < 0.001) and the diameter of the tubular ascending aorta (r = –0.44, p < 0.001). There was no significant correlation between the stretching and the dimension of the aortic root (r = –0.11, p = 0.239). There was a statistically significant (p < 0.001) difference in the longitudinal aortic stretching values between patients with a normal aortic valve (10.6 ±3.1 mm) and an aortic valve pathology (8.0 ±3.2 mm in all patients with an aortic valve pathology; 7.5 ±4.3 mm in isolated aortic stenosis, 8.5 ±2.9 mm in the case of isolated insufficiency, 8.2 ±2.8 mm for valves that were both stenotic and insufficient).ConclusionsSystolic aortic stretching negatively correlates with the diameter of the tubular ascending aorta and the age of the patients, and does not correlate with the diameter of the aortic root. It is lower in patients with an aortic valve pathology.