Articles de revues : « Aortic valve stenosis (AVS) »

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Frank, Rolf Dario, Regina Lanzmich, Philipp K. Haager et Ulrich Budde. « Severe Aortic Valve Stenosis ». Clinical and Applied Thrombosis/Hemostasis 23, n^o 3 (4 août 2016) : 229–34. http://dx.doi.org/10.1177/1076029616660759.

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Aortic valve stenosis (AVS) is the most common valve disease in adults. Severe forms are associated with acquired von Willebrand syndrome (aVWS) with loss of the largest von Willebrand factor (VWF) multimers. Diagnostic gold standard is the VWF multimer analysis. Valve replacement rapidly restores the VWF structure. Uncertainty exists if this effect is permanent and how functional VWF assays perform compared with multimer analysis. We studied 21 consecutive patients with severe AVS before and 6 to 18 months after valve surgery and compared them with 14 controls without valve disease referred for coronary angiography. The VWF multimers, VWF antigen (VWF:Ag), VWF collagen binding capacity (VWF:CB), VWF:CB/VWF:Ag ratio, in vitro bleeding time (PFA-100), factor VIII coagulation activity (FVIII:C), and VWF ristocetin cofactor activity (VWF:RCo) were determined. In all patients with AVS, the large VWF multimers were strongly reduced (56 ± 13% of normal plasma); all controls had normal multimers. The PFA-100 collagen/ADP closure times (coll/ADP CT) were prolonged in patients with AVS compared with the controls (175 ± 56 seconds vs 86 ± 14 seconds, P < .001). The VWF:CB/VWF:Ag ratio was pathological in 20 of the 21 patients but normal in controls. After surgery, the multimers normalized in all patients and coll/ADP CT shortened (pre 184 ± 65 seconds vs post 102 ± 22 seconds; P < .001). The VWF:CB/VWF:Ag ratio strongly improved ( P < .001) and normalized in 14 of 17 patients. In conclusion, all consecutive patients with severe AVS had an aVWS. The combination of coll/ADP CT and VWF:CB/VWF:Ag ratio detected the aVWS in all patients. More than 6 months after valve replacement, the VWF multimers were still normalized in all patients indicating a permanent cure of the aVWS.

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Rakhmanov, Yeltay, Paolo Enrico Maltese, Alessandra Zulian, Stefano Paolacci, Tommaso Beccari, Munis Dundar et Matteo Bertelli. « Genetic testing for aortic valve stenosis ». EuroBiotech Journal 2, s1 (1 septembre 2018) : 61–63. http://dx.doi.org/10.2478/ebtj-2018-0040.

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Abstract Aortic valve stenosis (AVS) is a congenital aortic defect in which the aortic lumen narrows due to thickening or calcification of the aortic valve without obstructing left ventricular outflow. Depending on the site of obstruction, AVS is classified as valvular, sub-valvular or supra-valvular. The prevalence of AVS is about 3% and increases with age. One in eight persons over the age of 75 years has moderate or severe AVS. AVS has autosomal dominant inheritance. It can be associated with mutations in the following genes: NOTCH1, SMAD6, SMAD4, and ELN. This Utility Gene Test was developed on the basis of the analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials, when available.

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Sossong, Verena, Thomas Helbing, Friedhelm Beyersdorf, Manfred Olschewski, Christoph Bode, Philipp Diehl, Ferenc Nagy et Martin Moser. « Increased levels of circulating microparticles in patients with severe aortic valve stenosis ». Thrombosis and Haemostasis 99, n^o 04 (2008) : 711–19. http://dx.doi.org/10.1160/th07-05-0334.

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SummaryThe mechanisms of the progression of aortic valve stenosis are unknown. The involvement of mononuclear cells and of chronic systemic inflammation has been suggested by analysis of pathological specimens. We hypothesize that shear stress caused by the constricted aortic orifice contributes to systemic proinflammation by activation of circulating blood cells and thereby generation of microparticles. Using flow cytometry we analyzed 22 patients with severe aortic valve stenosis (AVS) and 18 patient controls for the generation of circulating microparticles from platelet-(PMPs: CD31+/CD61+ or CD62P+), leukocyte-(LMPs: CD11b+) and endothelial cell (EMPs: CD62E+) origin. Apart from the constricted valve orifice groups were similar. PMPs were increased in AVS patients and their number correlated with valvular shear stress. Monocytes were activated in AVS patients, an observation that was also reflected by increased numbers of LMPs and by the detection of PMP-monocyte conjugates. Furthermore, EMPs reflecting the activation of endothelial cells but also conferring systemic inflammatory activity were increased in AVS patients and correlated with the number of activated monocytes. In conclusion, we show that AVS is accompanied by increased levels of microparticles and that shear stress can induce the formation of microparticles. Based on our results and histologic findings of other investigators the speculation that shear stress related to aortic valve stenosis induces a vicious circle including the generation of PMPs, the subsequent activation of monocytes and LMPs and finally the activation of endothelial cells contributing to the progress of aortic valve stenosis appears to be justified.

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Oostveen, Reindert F., Yannick Kaiser, Erik S. G. Stroes et Hein J. Verberne. « Molecular Imaging of Aortic Valve Stenosis with Positron Emission Tomography ». Pharmaceuticals 15, n^o 7 (30 juin 2022) : 812. http://dx.doi.org/10.3390/ph15070812.

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Aortic valve stenosis (AVS) is an increasingly prevalent disease in our aging population. Although multiple risk factors for AVS have been elucidated, medical therapies capable of slowing down disease progression remain unavailable. Molecular imaging technologies are opening up avenues for the non-invasive assessment of disease progression, allowing the assessment of (early) medical interventions. This review will focus on the role of positron emission tomography of the aortic valve with 18F-fluorodeoxyglucose and 18F-sodium fluoride but will also shed light on novel tracers which have potential in AVS, ranging from the healthy aortic valve to end-stage valvular disease.

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Schnitzler, Johan G., Lubna Ali, Anouk G. Groenen, Yannick Kaiser et Jeffrey Kroon. « Lipoprotein(a) as Orchestrator of Calcific Aortic Valve Stenosis ». Biomolecules 9, n^o 12 (21 novembre 2019) : 760. http://dx.doi.org/10.3390/biom9120760.

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Aortic valve stenosis (AVS) is the most prevalent valvular heart disease in the Western World with exponentially increased incidence with age. If left untreated, the yearly mortality rates increase up to 25%. Currently, no effective pharmacological interventions have been established to treat or prevent AVS. The only treatment modality so far is surgical or transcatheter aortic valve replacement (AVR). Lipoprotein(a) [Lp(a)] has been implicated as a pivotal player in the pathophysiology of calcification of the valves. Patients with elevated levels of Lp(a) have a higher risk of hospitalization or mortality due to the presence of AVS. Multiple studies indicated Lp(a) as a likely causal and independent risk factor for AVS. This review discusses the most important findings and mechanisms related to Lp(a) and AVS in detail. During the progression of AVS, Lp(a) enters the aortic valve tissue at damaged sites of the valves. Subsequently, autotaxin converts lysophosphatidylcholine in lysophosphatidic acid (LysoPA) which in turn acts as a ligand for the LysoPA receptor. This triggers a nuclear factor-κB cascade leading to increased transcripts of interleukin 6, bone morphogenetic protein 2, and runt-related transcription factor 2. This progresses to the actual calcification of the valves through production of alkaline phosphatase and calcium depositions. Furthermore, this review briefly mentions potentially interesting therapies that may play a role in the treatment or prevention of AVS in the near future.

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Bardelli, Moreno, Monica Cavressi, Giulia Furlanis, Bruno Pinamonti, Mariafontana Leone, Stefano Albani, Renata Korcova, Bruno Fabris et Gianfranco Sinagra. « Relationship between aortic valve stenosis and the hemodynamic pattern in the renal circulation, and restoration of the flow wave profile after correction of the valvular defect ». Journal of International Medical Research 48, n^o 9 (septembre 2020) : 030006052095690. http://dx.doi.org/10.1177/0300060520956907.

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Objective The index of maximal systolic acceleration ([AImax]: maximal systolic acceleration of the Doppler waveform divided by peak systolic velocity) shows diagnostic accuracy in screening of renal artery stenosis. This study aimed to determine whether an upstream factor of resistance, such as aortic valve stenosis (AVS), can affect Doppler parameters detected in the peripheral arteries. Methods In this prospective study, we measured the AImax in non-stenotic renal interlobar arteries of 62 patients with AVS. Patients were divided into three groups on the basis of severity of valvulopathy as follows: mild-to-moderate AVS (M-AVS; n = 24), intermediate AVS (I-AVS; n = 15), and severe AVS (S-AVS; n = 23) based on Nishimura’s criteria. Results The AImax in the renal parenchymal arteries was significantly lower in the S-AVS group (8.9 ± 3.6 s−1) than in the M-AVS (15.3 ± 3.8 s−1) and I-AVS groups (16.7 ± 5.2 s−1). The AImax was positively correlated with the aortic valve area and inversely correlated with the tranvalvular aortic pressure gradient. After aortic valve replacement, the AImax significantly increased from 10.7 ± 4.0 s−1 at baseline to 19.3 ± 4.4 s−1. Conclusions Proximal resistance can lead to diagnostic bias of Doppler parameters that are applied in the diagnosis of peripheral vasculopathies, particularly in renal artery stenosis.

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Artiach, Gonzalo, Miguel Carracedo, Till Seime, Oscar Plunde, Andres Laguna-Fernandez, Ljubica Matic, Anders Franco-Cereceda et Magnus Bäck. « Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification ». Cells 9, n^o 3 (11 mars 2020) : 684. http://dx.doi.org/10.3390/cells9030684.

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Aortic valve stenosis (AVS), a consequence of increased fibrosis and calcification of the aortic valve leaflets, causes progressive narrowing of the aortic valve. Proteoglycans, structural components of the aortic valve, accumulate in regions with fibrosis and moderate calcification. Particularly, proteoglycan 4 (PRG4) has been identified in fibrotic parts of aortic valves. However, the role of PRG4 in the context of AVS and aortic valve calcification has not yet been determined. Here, transcriptomics, histology, and immunohistochemistry were performed in human aortic valves from patients undergoing aortic valve replacement. Human valve interstitial cells (VICs) were used for calcification experiments and RNA expression analysis. PRG4 was significantly upregulated in thickened and calcified regions of aortic valves compared with healthy regions. In addition, mRNA levels of PRG4 positively associated with mRNA for proteins involved in cardiovascular calcification. Treatment of VICs with recombinant human PRG4 enhanced phosphate-induced calcification and increased the mRNA expression of bone morphogenetic protein 2 and the runt-related transcription factor 2. In summary, PRG4 was upregulated in the development of AVS and promoted VIC osteogenic differentiation and calcification. These results suggest that an altered valve leaflet proteoglycan composition may play a role in the progression of AVS.

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Ferrari, V., C. Mazzanti et L. De Biase. « RELATION BETWEEN CALCIUM METABOLISM AND DEVELOPMENT OF AORTIC VALVE STENOSIS ». European Heart Journal Supplements 26, Supplement_2 (avril 2024) : ii209. http://dx.doi.org/10.1093/eurheartjsupp/suae036.501.

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Abstract The role of calcium metabolism in the development of degenerative Aortic Valve Stenosis (AVS) is not completely understood. Valvular cell modifications and passive calcification can be both involved in the diseases. Vitamin D (Vit D) and Parathyroid Hormone (PTH) are important factor in calcium regulation and data on their modification in AVS are scanty. Their potential role in AVS prevention is not yet identified. Osteocalcin can be considered a marker of calcification and its potential usefulness in identification of patient at risk for AVS was not studied. In order to correlate calcium metabolism to AVS development we have studied PTH, Vit D and Osteocalcin in a population of patients with AVS. We recruited 100 patients admitted in our Cardiac Surgery Unit for AVS confirmed by electrocardiogram, echocardiogram and hemodynamic evaluation. Subjects with rheumatic or congenital valvulopathy and infectious endocarditis were excluded from the study. Calcium, phosphorus, calcium–phosphorus ratio (Ca/P ratio), PTH, Vit D, renal function and osteocalcin were measured in each patient. In our population, 93.5% of patients had low levels of Vit D (<30 ng / ml), 42.4% had elevated levels of PTH (>38.4 pg / ml) and 28% had low levels of osteocalcin (<14 ng / ml). 87% of the population had normal calcium levels (8.4–10.2 mg / dl) and 93.3% had normal levels of phosphoremia (2.7–4.5 mg / dl). Defining as normal a Ca/P ratio between 1.5 and 2.5, 60.7% of our population had high levels of Ca/P. In conclusion, our findings suggest that patients suffering from AVS have abnormal levels of factors involved in the regulation of calcium metabolism. Some factors can be target for preventive therapies.

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Krzesińska, Aleksandra, Maria Nowak, Agnieszka Mickiewicz, Gabriela Chyła-Danił, Agnieszka Ćwiklińska, Olga M. Koper-Lenkiewicz, Joanna Kamińska et al. « Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve ». Biomedicines 11, n^o 7 (25 juin 2023) : 1823. http://dx.doi.org/10.3390/biomedicines11071823.

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Bicuspid aortic valve (BAV) affects 0.5–2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.

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Torres-Arellano, José M., Juan C. Echeverría, Nydia Ávila-Vanzzini, Rashidi Springall, Andrea Toledo, Oscar Infante, Rafael Bojalil, Jorge E. Cossío-Aranda, Erika Fajardo et Claudia Lerma. « Cardiac Autonomic Response to Active Standing in Calcific Aortic Valve Stenosis ». Journal of Clinical Medicine 10, n^o 9 (7 mai 2021) : 2004. http://dx.doi.org/10.3390/jcm10092004.

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Aortic stenosis is a progressive heart valve disorder characterized by calcification of the leaflets. Heart rate variability (HRV) analysis has been proposed for assessing the heart response to autonomic activity, which is documented to be altered in different cardiac diseases. The objective of the study was to evaluate changes of HRV in patients with aortic stenosis by an active standing challenge. Twenty-two volunteers without alterations in the aortic valve (NAV) and twenty-five patients diagnosed with moderate and severe calcific aortic valve stenosis (AVS) participated in this cross-sectional study. Ten minute electrocardiograms were performed in a supine position and in active standing positions afterwards, to obtain temporal, spectral, and scaling HRV indices: mean value of all NN intervals (meanNN), low-frequency (LF) and high-frequency (HF) bands spectral power, and the short-term scaling indices (α1 and αsign1). The AVS group showed higher values of LF, LF/HF and αsign1 compared with the NAV group at supine position. These patients also expressed smaller changes in meanNN, LF, HF, LF/HF, α1, and αsign1 between positions. In conclusion, we confirmed from short-term recordings that patients with moderate and severe calcific AVS have a decreased cardiac parasympathetic supine response and that the dynamic of heart rate fluctuations is modified compared to NAV subjects, but we also evidenced that they manifest reduced autonomic adjustments caused by the active standing challenge.

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Perpétuo, Luís, António S. Barros, Jéssica Dalsuco, Rita Nogueira-Ferreira, Pedro Resende-Gonçalves, Inês Falcão-Pires, Rita Ferreira, Adelino Leite-Moreira, Fábio Trindade et Rui Vitorino. « Coronary Artery Disease and Aortic Valve Stenosis : A Urine Proteomics Study ». International Journal of Molecular Sciences 23, n^o 21 (5 novembre 2022) : 13579. http://dx.doi.org/10.3390/ijms232113579.

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Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).

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Manchester, Emily L., Selene Pirola, Mohammad Yousuf Salmasi, Declan P. O’Regan, Thanos Athanasiou et Xiao Yun Xu. « Analysis of Turbulence Effects in a Patient-Specific Aorta with Aortic Valve Stenosis ». Cardiovascular Engineering and Technology 12, n^o 4 (7 avril 2021) : 438–53. http://dx.doi.org/10.1007/s13239-021-00536-9.

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Abstract Blood flow in the aorta is often assumed laminar, however aortic valve pathologies may induce transition to turbulence and our understanding of turbulence effects is incomplete. The aim of the study was to provide a detailed analysis of turbulence effects in aortic valve stenosis (AVS). Methods Large-eddy simulation (LES) of flow through a patient-specific aorta with AVS was conducted. Magnetic resonance imaging (MRI) was performed and used for geometric reconstruction and patient-specific boundary conditions. Computed velocity field was compared with 4D flow MRI to check qualitative and quantitative consistency. The effect of turbulence was evaluated in terms of fluctuating kinetic energy, turbulence-related wall shear stress (WSS) and energy loss. Results Our analysis suggested that turbulence was induced by a combination of a high velocity jet impinging on the arterial wall and a dilated ascending aorta which provided sufficient space for turbulence to develop. Turbulent WSS contributed to 40% of the total WSS in the ascending aorta and 38% in the entire aorta. Viscous and turbulent irreversible energy losses accounted for 3.9 and 2.7% of the total stroke work, respectively. Conclusions This study demonstrates the importance of turbulence in assessing aortic haemodynamics in a patient with AVS. Neglecting the turbulent contribution to WSS could potentially result in a significant underestimation of the total WSS. Further work is warranted to extend the analysis to more AVS cases and patients with other aortic valve diseases.

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Echeverría, Juan C., Nydia Ávila-Vanzzini, Rashidi Springall, José M. Torres-Arellano, Andrea Toledo, Oscar Infante, Rafael Bojalil, Jorge Cossío, Erika Fajardo et Claudia Lerma. « Inflammation and Reduced Parasympathetic Cardiac Modulation in Aortic-Valve Sclerosis ». Applied Sciences 9, n^o 19 (26 septembre 2019) : 4020. http://dx.doi.org/10.3390/app9194020.

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Aortic-valve sclerosis increases cardiovascular mortality risk and precedes aortic-valve stenosis, but its mechanisms are not well understood. The purpose of this study was to compare the cardiac autonomic modulation and inflammation markers between subjects with aortic-valve normal leaflets and subjects with aortic-valve sclerosis. According to 2-D transthoracic echocardiograms, 61 middle-aged volunteers without chronic or acute illnesses were classified in two groups: with no aortic-valve sclerosis (NAVS, N = 16) and with aortic-valve sclerosis (AVS, N = 45). An electrocardiogram at the supine position and active standing was collected to estimate heart rate variability (HRV) indices. A blood sample was obtained to quantify markers of inflammation. Compared to NAVS, AVS subjects showed higher levels of IL-6 (1619 ± 650 vs. 1169 ± 676 pg/mL, p = 0.044) as well as TNFα (370.8 ± 182.0 vs. 247.3 ± 188.2 pg/mL, p = 0.032), and larger low-frequency (LF) to high-frequency (HF) ratio during supine position (Ln(LF/HF) = 0.85 ± 0.85 vs. 0.11 ± 0.69, p = 0.003). Multiple logistic regression analysis showed that AVS was independently associated with LF/HF, TNFα and left ventricle mass index (p < 0.05). In conclusion, a significant reduction of the parasympathetic-driven cardiac modulation and low-grade inflammation occurs in aortic-valve sclerosis.

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Matilla, Lara, Eva Jover, Mattie Garaikoetxea, Ernesto Martín-Nuñez, Vanessa Arrieta, Amaia García-Peña, Adela Navarro et al. « Sex-Related Signaling of Aldosterone/Mineralocorticoid Receptor Pathway in Calcific Aortic Stenosis ». Hypertension 79, n^o 8 (août 2022) : 1724–37. http://dx.doi.org/10.1161/hypertensionaha.122.19526.

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Background: There are sex differences in the pathophysiology of aortic valve (AV) calcification in patients with aortic stenosis, although the molecular and cellular mechanisms have not been elucidated. Aldosterone (Aldo) promotes proteoglycan synthesis in valve interstitial cells (VICs) from mitral valves via the mineralocorticoid receptor (MR). We investigated the influence of sex in the role of Aldo/MR pathway in AV alterations in patients with aortic stenosis. METHODS AND RESULTS: MR was expressed by primary aortic VICs and in AVs from patients with aortic stenosis. MR expression positively correlated with VIC activation markers in AVs from both sexes. However, MR expression was positively associated with molecules involved in AV calcification only in AV from men. Aldo enhanced VIC activation markers in cells from men and women. Interestingly, Aldo increased the expression of calcification markers only in VICs isolated from men. In female VICs, Aldo enhanced fibrotic molecules. MR antagonism (spironolactone) blocked all the above effects. Cytokine arrays showed ICAM (intercellular adhesion molecule)-1 and osteopontin to be specifically increased by Aldo in male VICs. In AVs from men, MR expression positively associated with both ICAM-1 (intercellular adhesion molecule-1) and osteopontin. Only in female VICs, estradiol treatment blocked Aldo-induced VICs activation, inflammation, and fibrosis. Conclusions: These findings demonstrate that the Aldo/MR pathway could play a role in early stages of aortic stenosis by promoting VICs activation, fibrosis, and ulterior calcification. Importantly, Aldo/MR pathway is involved in fibrosis in women and in early AV calcification only in men. Accordingly, MR antagonism emerges as a new sex-specific pharmacological treatment to prevent AV alterations.

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Gebhard, C., F. Maafi, B. Stähli, A. Bonnefoy, C. Gebhard, W. Nachar, A. de Oliveira Moraes et al. « Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis ». Thrombosis and Haemostasis 118, n^o 02 (2018) : 288–97. http://dx.doi.org/10.1160/th17-10-0729.

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Background Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown. Methods and Results We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS (n = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls (p < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations (r = 0.3, p = 0.018 and r = −0.4, p = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS (r = −0.3, p = 0.045). Conclusion Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS.

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Lassalle, Fanny, Mickael Rosa, Bart Staels, Eric Van Belle, Sophie Susen et Annabelle Dupont. « Circulating Monocyte Subsets and Transcatheter Aortic Valve Replacement ». International Journal of Molecular Sciences 23, n^o 10 (10 mai 2022) : 5303. http://dx.doi.org/10.3390/ijms23105303.

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Transcatheter aortic valve replacement (TAVR), as an alternative to open heart surgery, has revolutionized the treatment of severe aortic valve stenosis (AVS), the most common valvular disorder in the elderly. AVS is now considered a form of atherosclerosis and, like the latter, partly of inflammatory origin. Patients with high-grade AVS have a highly disturbed blood flow associated with high levels of shear stress. The immediate reopening of the valve during TAVR leads to a sudden restoration of a normal blood flow hemodynamic. Despite its good prognosis for patients, TAVR remains associated with bleeding or thrombotic postprocedural complications, involving mechanisms that are still poorly understood. Many studies report the close link between blood coagulation and inflammation, termed thromboinflammation, including monocytes as a major actor. The TAVR procedure represents a unique opportunity to study the influence of shear stress on human monocytes, key mediators of inflammation and hemostasis processes. The purpose of this study was to conduct a review of the literature to provide a comprehensive overview of the impact of TAVR on monocyte phenotype and subset repartition and the association of these parameters with the clinical outcomes of patients with severe AVS who underwent TAVR.

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Peeters, Frederique E. C. M., Bas L. J. H. Kietselaer, Judith Hilderink, Noreen van der Linden, Marijke Niens, Harry J. G. M. Crijns et Steven J. R. Meex. « Biological variation of cardiac markers in patients with aortic valve stenosis ». Open Heart 6, n^o 1 (mai 2019) : e001040. http://dx.doi.org/10.1136/openhrt-2019-001040.

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ObjectiveCardiac biomarkers hold promise for follow-up and management of aortic valve stenosis (AVS). When interpreting serial biomarker measurements of patients with AVS, it can be challenging to distinguish ‘real changes’ from ‘random fluctuation’. Hence, robust estimation of the biological variation of these biomarkers is essential. In the present study we assessed biological variation of B-type natriuretic peptide (BNP), N-terminus pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-T and high-sensitivity troponin-I (hs-TnT and hs-TnI), and ST2 in subjects with stable AVS.MethodsSerial blood sampling was performed in 25 subjects with moderate AVS—confirmed by echocardiography—and all free from acute cardiovascular events in the past 6 months. Blood samples were taken on seven standardised occasions during 1 year. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II) and reference change values were calculated for all cardiac biomarkers.ResultsCVI was highest for BNP (62.0%, 95% CI 52.5 to 75.4) and lowest for hs-TnI (9.2%, 95% CI 2.8 to 13.8). CVG exceeded the CVI for all biomarkers except BNP, and ranged from 19.8% (95% CI 13.8 to 33.4) for ST2 to 57.2% (95% CI 40.4 to 97.3) for hs-TnT. NT-proBNP, hs-TnT and ST2 revealed CVA <5%, while BNP and hs-TnI showed a higher CVA (19.7 and 14.9, respectively). All biomarkers except BNP showed marked individuality, with II ranging from 0.21 to 0.67 (BNP 1.34).ConclusionThis study provides the first biological variation estimates of cardiac biomarkers in patients with stable AVS. These estimates allow a more evidence-based interpretation of biomarker changes in the follow-up and management of patients with AVS.Trial registration numberNCT02510482

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Irtyuga, O. B., E. V. Zhiduleva, E. E. Kazakova et O. M. Moiseeva. « PATHOGENESIS OF AORTIC STENOSIS IN HYPERTENSIVE PATIENTS ». "Arterial’naya Gipertenziya" ("Arterial Hypertension") 19, n^o 6 (28 décembre 2013) : 495–501. http://dx.doi.org/10.18705/1607-419x-2013-19-6-495-501.

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Objective. To assess osteoprotegerin (OPG) and soluble ligand receptor activator of transcription factor kappa-B (RANKL) levels in patients with aortic stenosis and systemic hypertension.Design and methods. Sixty-one patients with aortic valve stenosis (AVS) [31 patients with bicuspid aortic valve (BAV) and 30 patients with tricuspid aortic valve (TAV)] were examined. Thirty-two patients without heart diseases formed the control group. Serum levels of C-reactive protein, ОPG, sRANKL and lipid profile were assessed in all patients.Results. Elevated blood pressure (BP) was found in 93 % patients with TAV and in 71 % patients with BAV. Serum concentration of OPG was increased in patients with TAV and BAV vs control group. OPG concentration was negatively correlated with BP level only in patients with TAV. sRANKL level was increased only in patients with BAV. At the same time sRANKL level positively correlated with BP in patients with TAV. Conclusion. Systemic hypertension is the key risk factor for OPG/RANKL/RANK system activation in patients without congenital heart disease.

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Vieceli Dalla Sega, Francesco, Francesca Fortini, Paolo Cimaglia, Luisa Marracino, Elisabetta Tonet, Antonio Antonucci, Marco Moscarelli, Gianluca Campo, Paola Rizzo et Roberto Ferrari. « COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification ». International Journal of Molecular Sciences 21, n^o 23 (24 novembre 2020) : 8917. http://dx.doi.org/10.3390/ijms21238917.

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Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-β-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.

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Yalta, Kenan, Orkide Palabiyik, Muhammet Gurdogan et Yekta Gurlertop. « Serum copeptin might improve risk stratification and management of aortic valve stenosis : a review of pathophysiological insights and practical implications ». Therapeutic Advances in Cardiovascular Disease 13 (janvier 2019) : 175394471982642. http://dx.doi.org/10.1177/1753944719826420.

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Over recent decades, the prevalence of aortic valve stenosis (AVS) has been constantly increasing possibly owing to the aging of general population. Severe AVS as determined by an aortic valve area (AVA) of <1 cm2 has been regarded as a serious clinical condition potentially associated with a variety of adverse outcomes, including sudden cardiac death (SCD). However, patients with severe AVS (in the absence of overt high-risk features) are usually evaluated and managed exclusively based on symptomatology or imperfect prognostic tools including exercise testing and biomarkers, with a potential risk of mismanagement, suggesting the need for further objective risk stratifiers in this setting. Within this context, copeptin (C-terminal pro-vasopressin), a novel neurohormone widely considered as the surrogate marker of the arginine–vasopressin (AVP) system, may potentially serve as a reliable prognostic and therapeutic guide (e.g. timing of aortic valvular intervention) in patients with severe AVS largely based on its hemodynamic, fibrogenic as well as autonomic implications in these patients. Accordingly, the present paper aims to discuss clinical and pathophysiological implications of copeptin in the setting of AVS along with a summary of biomarkers and other prognostic tools used in this setting.

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Artiach, Gonzalo, Miguel Carracedo, Oscar Plunde, Craig E. Wheelock, Silke Thul, Peter Sjövall, Anders Franco-Cereceda, Andres Laguna-Fernandez, Hildur Arnardottir et Magnus Bäck. « Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis ». Circulation 142, n^o 8 (25 août 2020) : 776–89. http://dx.doi.org/10.1161/circulationaha.119.041868.

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Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in cardiovascular prevention have recently been demonstrated in a large randomized, controlled trial. In addition, n-3 PUFAs serve as the substrate for the synthesis of specialized proresolving mediators, which are known by their potent beneficial anti-inflammatory, proresolving, and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and specialized proresolving mediators on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA–derived specialized proresolving mediators in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe −/− mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in noncalcified regions compared with calcified regions. Liquid chromatography tandem mass spectrometry–based lipid mediator lipidomics identified that the n-3 PUFA–derived specialized proresolving mediator resolvin E1 was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe −/− mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1 tg ×Apoe −/− ), which enables the endogenous synthesis of n-3 PUFA and increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization, and improved echocardiographic parameters. Finally, abrogation of the resolvin E1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1 tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived resolvin E1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.

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Conte, Maddalena, Paolo Poggio, Maria Monti, Laura Petraglia, Serena Cabaro, Dario Bruzzese, Giuseppe Comentale et al. « Isolated Valve Amyloid Deposition in Aortic Stenosis : Potential Clinical and Pathophysiological Relevance ». International Journal of Molecular Sciences 25, n^o 2 (18 janvier 2024) : 1171. http://dx.doi.org/10.3390/ijms25021171.

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Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

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Al Hageh, Cynthia, Ryan Rahy, Georges Khazen, Francois Brial, Rony S. Khnayzer, Dominique Gauguier et Pierre A. Zalloua. « Plasma and urine metabolomic analyses in aortic valve stenosis reveal shared and biofluid-specific changes in metabolite levels ». PLOS ONE 15, n^o 11 (25 novembre 2020) : e0242019. http://dx.doi.org/10.1371/journal.pone.0242019.

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Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly.

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HIGUCHI, Maria de Lourdes, Marilia Harumi HIGUCHI-DOS-SANTOS, Humberto PIERRI, Sueli PALOMINO, Nadia Vieira SAMBIASE, José Antonio Franchini RAMIRES et Maurício WAJNGARTEN. « Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves ». Revista do Instituto de Medicina Tropical de São Paulo 44, n^o 4 (juillet 2002) : 209–12. http://dx.doi.org/10.1590/s0036-46652002000400005.

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Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.

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Sever, Matjaž, Samo Ribarič et Marjan Kordaš. « Simulation of Exercise-Induced Syncope in a Heart Model with Severe Aortic Valve Stenosis ». Computational and Mathematical Methods in Medicine 2012 (2012) : 1–9. http://dx.doi.org/10.1155/2012/138401.

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Severe aortic valve stenosis (AVS) can cause an exercise-induced reflex syncope (RS). The precise mechanism of this syncope is not known. The changes in hemodynamics are variable, including arrhythmias and myocardial ischemia, and one of the few consistent changes is a sudden fall in systemic and pulmonary arterial pressures (suggesting a reduced vascular resistance) followed by a decline in heart rate. The contribution of the cardioinhibitory and vasodepressor components of the RS to hemodynamics was evaluated by a computer model. This lumped-parameter computer simulation was based on equivalent electronic circuits (EECs) that reflect the hemodynamic conditions of a heart with severe AVS and a concomitantly decreased contractility as a long-term detrimental consequence of compensatory left ventricular hypertrophy. In addition, the EECs model simulated the resetting of the sympathetic nervous tone in the heart and systemic circuit during exercise and exercise-induced syncope, the fluctuating intra-thoracic pressure during respiration, and the passive relaxation of ventricle during diastole. The results of this simulation were consistent with the published case reports of exertional syncope in patients with AVS. The value of the EEC model is its ability to quantify the effect of a selective and gradable change in heart rate, ventricular contractility, or systemic vascular resistance on the hemodynamics during an exertional syncope in patients with severe AVS.

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MUKANOVA, M. B., F. YU KOPYLOV, R. N. KOMAROV, I. I. SEREBRENNIKOV, F. S. GAFUROV, A. N. KHUZIAKHMEDOV, N. M. BABAKULOVA et A. M. ISMAILBAEV. « Acute coronary syndrome in patients with aortic valve stenosis ». Practical medicine 21, n^o 2 (2023) : 73–78. http://dx.doi.org/10.32000/2072-1757-2023-2-73-78.

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The purpose — to assess the acute coronary syndrome (ACS) clinical aspects in patients with aortic stenosis. Material and methods. This is a retrospective single-center study that included comparison of hospital and midterm outcomes of ACS and aortic stenosis (n = 95, divided into the following groups: group 1 — severe aortic stenosis + ACS (n = 39); group 2 — moderate aortic stenosis + ACS (n = 28); group 3 — ACS without aortic stenosis (the control group selected using «Propensity matching» method) (n = 28)). Results. Hospital mortality did not differ statistically between the groups. In group 1, there was a tendency to worse survival within 1 year. In groups with aortic malformation, ACS with ST segment elevation was less common — p = 0.0002 and p = 0.001, respectively. In group 1, 23.1% of patients had intact coronary arteries. Conclusions. Severe aortic valve stenosis in some cases «mimics» acute coronary syndrome, which is indicated by significantly more frequent detection of intact coronary arteries in this cohort. Aortic stenosis of varying degrees does not lead to an increase in the frequency of early postoperative complications and 30-day mortality after PCI.

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Marshafawy, Hala Al, Gehan Attia Al Sawah, Mona Hafez, Mohammed Matter, Adel El Gamal, Abdel Gawad Sheishaa et Magdy Abu El Kair. « Balloon Valvuloplasty of Aortic Valve Stenosis in Childhood : Midterm Results in a Children's Hospital, Mansoura University, Egypt ». Clinical Medicine Insights : Cardiology 6 (janvier 2012) : CMC.S8602. http://dx.doi.org/10.4137/cmc.s8602.

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Background Balloon valvuloplasty was established as an alternative to surgery for treatment of aortic valve stenosis in childhood. Acute complications after balloon dilatation including aortic insufficiency or early death were described. Aim of Work To analyze early outcome and midterm results of balloon aortic valvuloplasty (BAV) in Children's Hospital, Mansoura University, Egypt. Subjects and Methods Between April 2005–June 2008, all consecutive patients of age <18 years treated for aortic valve stenosis (AVS) with BAV were analyzed retrospectively. The study included 21 patients; 17 males, and 4 females. Their age ranged from the neonatal period to 10 years (mean age 5.6 ± 3.7 years). Patients with gradient ≥50 mmHg and aortic valve insufficiency (AI) up to grade I were included. All patients had isolated aortic valve stenosis except 3 patients (14.3%) had associated aortic coarctation. Six patients (28.6%) had bicuspid aortic valve. All patients had normal myocardial function except one (4.8%) had FS 15%. The duration of follow up was (mean ± SD: 18.5 ± 11.7 months). Results Femoral artery approach was used in 20 patients (95.2%) and carotid artery in one neonate (4.8%). Balloon/annulus ratio was 0.83 ± 0.04. Significant reduction in pressure gradient was achieved (mean 66.7 ± 9.8 mmHg to 20.65 ± 2.99 mmHg) ( P < 0.001). Nine patients (42.8%) developed grade I AI, 2 patients (9.5%) developed grade II AI and 1 patient (4.8%) developed grade III AI. Two early deaths (9.5%); one died due to heart failure caused by grade IV AI and a neonate died because of severely compromised LV function. One patient (4.8%) had femoral artery occlusion necessitating anticoagulation. Patients remained free from re-intervention during follow up. Conclusion Balloon valvuloplasty of aortic valve stenosis significantly reduces gradient with low morbidity and mortality in children.

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Gul, Yasar Gokhan, Selcuk Alver et Bahadir Ciftci. « A Case Report of a Pericapsular Nerve Group Block for Transcatheter Aortic Valve Implantation ». A&A Practice 17, n^o 12 (décembre 2023) : e01743. http://dx.doi.org/10.1213/xaa.0000000000001743.

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A pericapsular nerve group (PENG) block is an interfascial plane block that targets the articular branches of the femoral and obturator nerves. PENG blocks may be used for hip, vein, and groin surgeries. Transcatheter aortic valve implantation (TAVI) is a common treatment for aortic valve stenosis (AVS). Patients who undergo TAVI tend to be at high risk due to their older age and comorbidities. A PENG block using a high volume of local anesthetics may be as effective as a lumbar plexus block. In this case report, we describe successful anesthesia management using PENG blocks in 2 patients who underwent TAVI.

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Schnabel, Christian, Anett Jannasch, Saskia Faak, Thomas Waldow et Edmund Koch. « Imaging of aortic valve dynamics in 4D OCT ». Current Directions in Biomedical Engineering 1, n^o 1 (1 septembre 2015) : 254–56. http://dx.doi.org/10.1515/cdbme-2015-0063.

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AbstractThe mechanical components of the heart, especially the valves and leaflets, are enormous stressed during lifetime. Therefore, those structures undergo different pathophysiological tissue transformations which affect cardiac output and in consequence living comfort of affected patients. These changes may lead to calcific aortic valve stenosis (AVS), the major heart valve disease in humans. The knowledge about changes of the dynamic behaviour during the course of this disease and the possibility of early stage diagnosis is of particular interest and could lead to the development of new treatment strategies and drug based options of prevention or therapy. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behaviour of the murine aortic valve and to characterize dynamic properties during artificial stimulation. We present a promising tool to investigate the aortic valve dynamics in an ex vivo disease model with a high spatial and temporal resolution using a multimodal imaging setup.

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Fradejas-Sastre, Víctor, Paula Parás-Bravo, Manuel Herrero-Montes, María Paz-Zulueta, Ester Boixadera-Planas, Luis Manuel Fernández-Cacho, Gabriela Veiga-Fernández, Maria Elena Arnáiz-García et Jose María De-la-Torre-Hernández. « Surgical vs. transcatheter arotic valve replacement in patients over 75 years with aortic stenosis : sociodemographic profile, clinical characteristics, quality of life and functionality ». PeerJ 11 (20 septembre 2023) : e16102. http://dx.doi.org/10.7717/peerj.16102.

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Background Aortic valve stenosis (AVS) affects 25% of the population over 65 years. At present, there is no curative medical treatment for AVS and therefore the surgical approach, consisting of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), is the treatment of choice. Methodology The aim of this study was to analyze the sociodemographic and clinical characteristics, quality of life and functionality of a sample of patients with AVS over 75 years of age, who underwent TAVR or SAVR, applying standard clinical practice. A prospective multicenter observational study was conducted in two hospitals of the Spanish National Health System. Data were collected at baseline, 1, 6 months and 1 year. Results In total, 227 participants were included, with a mean age of 80.6 [SD 4.1]. Statistically significant differences were found in terms of quality of life, which was higher at 1 year in patients who underwent SAVR. In terms of functionality, SAVR patients obtained a better score (p < 0.01). However, patients who underwent TAVR began with a worse baseline situation and managed to increase their quality of life and functionality after 1 year of follow-up. Conclusion The individualized choice of TAVR or SAVR in patients with AVS improves patients’ quality of life and function. Moreover, the TAVR procedure in patients with a worse baseline situation and a high surgical risk achieved a similar increase in quality of life and functionality compared to patients undergoing SAVR with a better baseline situation.

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Mühlenbruch, G., J. E. Wildberger, R. Koos, M. Das, C. Thomas, K. Ruhl, M. Niethammer et al. « Calcium scoring of aortic valve calcification in aortic valve stenosis with a multislice computed tomography scanner : non-enhanced versus contrast-enhanced studies ». Acta Radiologica 46, n^o 6 (octobre 2005) : 561–66. http://dx.doi.org/10.1080/02841850510021698.

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Purpose: Previous studies have shown a positive correlation between amount of aortic valve calcification (AVC) and degree of aortic valve stenosis (AVS). We have investigated whether calcium scoring of AVC from contrast-enhanced images is reliable. Material and Methods: Nineteen patients with suspected AVS underwent retrospectively ECG-gated multislice computed tomography (MSCT). Standardized scan protocols were applied prior to (120 KV, 133 mAseff) and after (120 KV, 500 mAseff) the administration of non-ionic contrast material. Image reconstruction was performed at 60% of the RR interval (slice thickness 3 mm, reconstruction increment 2 mm). AVC was quantified using Agatston score and calcium mass. The number of lesions was calculated. All non-enhanced images were scored using thresholds of 130 HU and 350 HU. Contrast-enhanced images were assessed with a threshold of 350 HU exclusively. Results: Fifteen patients with AVCs were included in the statistical analysis. The mean Agatston score (calcium mass) in non-enhanced images was 2888.4±2844.4 (694.2 mg±869.3 mg). Altering the threshold from 130 HU to 350 HU led to a 58.2% (30.5%) decrease in the AVC score ( P values <0.001). Contrast-enhanced images showed an increased Agatston score (calcium mass) of 56.2% (33.5%) compared to non-enhanced images ( P values <0.05) with the same threshold of 350 HU. Conclusion: Quantification of AVC from contrast-enhanced images is not reliable, as contrast material simulates calcification.

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Perrone, M. A., F. G. Viola, M. Minieri, S. Caporali, A. Copponi, G. Sancesario, S. Angeletti et al. « The Von Willebrand Factor Antigen Plasma Concentration : a Monitoring Marker in the Treatment of Aortic and Mitral Valve Diseases ». Folia Biologica 66, n^o 4 (2020) : 133–41. http://dx.doi.org/10.14712/fb2020066040133.

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Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.

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Huang, Ninghao, Zhenhuang Zhuang, Zhonghua Liu et Tao Huang. « Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis : A Prospective Cohort Study of 0.5 Million Participants ». Nutrients 14, n^o 11 (28 mai 2022) : 2273. http://dx.doi.org/10.3390/nu14112273.

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Background: Observational studies have shown that modifiable risk factors are associated with aortic valve stenosis (AVS). However, the causality behind these associations remains largely unknown. Objectives: To explore the associations of modifiable risk factors, including metabolic factors, biochemical measures, education, and lifestyles with AVS and their potential causal associations. Methods: We enrolled 361,930 British white people with genetic data in the UK biobank. Cox proportional risk regression models were used to estimate the hazard ratios between 28 modifiable risk factors and AVS. We used genetic instruments for modifiable risk factors to determine the potential causal relationships using a one-sample Mendelian randomization (MR) approach. Results: A total of 1602 participants developed AVS during an 8.4-year follow-up. Observational analyses showed higher adiposity, blood pressure, heart rate, low-density lipoprotein, urate, C-reactive protein, creatinine, albumin, and glycated hemoglobin, but lower serum vitamin D, and education, unhealthy lifestyle, and poor sleep quality were related to a higher risk of AVS after adjusting for the Bonferroni correction (p < 0.0013). Genetically predicted 1-SD higher levels of body mass index [HR: 1.09, 95% CI: 1.03 to 1.16], body fat percentage (1.17, 1.03 to 1.33), triglyceride (TG) [1.08, 1.00 to 1.16], low-density lipoprotein (LDL) (1.15, 1.08 to 1.21) and serum total cholesterol (TC) (1.13, 1.02 to 1.25) were associated with a higher risk of AVS, respectively. Genetically determined per category higher insomnia (1.32, 1.13 to 1.55) was also associated with AVS. The abovementioned genetic associations with the incident AVS showed an increasing relationship pattern. Conclusions: This study provides strong evidence for the potential causal roles of cardiometabolic factors in developing AVS, highlighting that an idea of metabolic status through a healthy lifestyle may help prevent AVS.

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Youssef, Ali, Mustafa Alrefae et Sayed Abouelsoud. « Spontaneous regression of severe aortic stenosis after massive embolization in a patient with antiphospholipid syndrome ». Seminars in Cardiovascular Medicine 25, n^o 1 (1 janvier 2019) : 4–8. http://dx.doi.org/10.2478/semcard-2019-0002.

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Summary We present a case of probably unreported aortic stenosis evolution in a patient with primary antiphospholipid syndrome (APS). A female patient, 54 years old, with a history of recurrent deep venous thrombosis, an episode of pulmonary embolism and was positive for APS antibodies. She was kept on warfarin and aspirin. The patient was admitted with acute pulmonary edema and severe aortic stenosis. While preparing for aortic valve surgery, the patient developed acute stroke, and a week later developed concurrent acute ischemia of both lower limbs. Emergency surgery salvaged the lower limbs and follow up transthoracic echocardiography showed marked regression of the thickening of the aortic valve leaflets, only mild aortic stenosis and moderate aortic regurgitation. Aortic valve surgery was cancelled, and the patient was kept on warfarin and aspirin. Conclusion Development of severe aortic stenosis is uncommon in primary APS, and this scenario of spontaneous improvement from a severe to a mild aortic stenosis, is probably unreported before.

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Aguado, Brian A., Katherine B. Schuetze, Joseph C. Grim, Cierra J. Walker, Anne C. Cox, Tova L. Ceccato, Aik-Choon Tan et al. « Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation ». Science Translational Medicine 11, n^o 509 (11 septembre 2019) : eaav3233. http://dx.doi.org/10.1126/scitranslmed.aav3233.

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The transcatheter aortic valve replacement (TAVR) procedure has emerged as a minimally invasive treatment for patients with aortic valve stenosis (AVS). However, alterations in serum factor composition and biological activity after TAVR remain unknown. Here, we quantified the systemic inflammatory effects of the TAVR procedure and hypothesized that alterations in serum factor composition would modulate valve and cardiac fibrosis. Serum samples were obtained from patients with AVS immediately before their TAVR procedure (pre-TAVR) and about 1 month afterward (post-TAVR). Aptamer-based proteomic profiling revealed alterations in post-TAVR serum composition, and ontological analysis identified inflammatory macrophage factors implicated in myofibroblast activation and deactivation. Hydrogel biomaterials used as valve matrix mimics demonstrated that post-TAVR serum reduced myofibroblast activation of valvular interstitial cells relative to pre-TAVR serum from the same patient. Transcriptomics and curated network analysis revealed a shift in myofibroblast phenotype from pre-TAVR to post-TAVR and identified p38 MAPK signaling as one pathway involved in pre-TAVR–mediated myofibroblast activation. Post-TAVR serum deactivated valve and cardiac myofibroblasts initially exposed to pre-TAVR serum to a quiescent fibroblast phenotype. Our in vitro deactivation data correlated with patient disease severity measured via echocardiography and multimorbidity scores, and correlations were dependent on hydrogel stiffness. Sex differences in cellular responses to male and female sera were also observed and may corroborate clinical observations regarding sex-specific TAVR outcomes. Together, alterations in serum composition after TAVR may lead to an antifibrotic fibroblast phenotype, which suggests earlier interventions may be beneficial for patients with advanced AVS to prevent further disease progression.

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Adel, Hani Mahmoud. « Evaluation of initial and medium-term follow-up results of balloon aortic valvuloplasty in severe aortic valve stenosis in newborns, infants and children in Alexandria, Egypt ». International Journal Of Community Medicine And Public Health 6, n^o 5 (27 avril 2019) : 1863. http://dx.doi.org/10.18203/2394-6040.ijcmph20191616.

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Background: Aortic valve stenosis (AVS) represents 3%–7% of all congenital heart diseases. Balloon aortic valvuloplasty (BAoV) has been established as an alternative to surgery for therapy of AVS in infants and children; and has proven to be an effective method for decreasing the gradient between the left ventricle and the aorta. The objective of the study was to evaluate the initial and medium-term results of BAoV in newborns, infants and children with severe AS, treated at the Alexandria University Children’s Hospital.Methods: Thirty-seven newborns, infants and children with severe AS treated by B AoV between 2009 and 2017 were studied. They were followed-up for at least 1year post- ballooning by clinical and echocardiographic evaluation.Results: The mean AoV annulus diameter by echo was 13.1±4.4 mm and by angiographic measurement was 12.8±4.3 mm. The mean Doppler gradient across AoV was 91.8±14.7 mmHg, compared to mean catheter gradient of 66.1±13.4 mmHg. The mean inflated balloon diameter was 12.1±4.1 mm. The mean balloon/AoV annulus ratio by angiogram was 0.94±0.03 (0.88–1). The mean pressure gradient across the AoV post-ballooning was 21.5±6.9 mmHg by Doppler and was 10.3±4.7 mmHg by catheter, both were significantly less than pre-ballooning values (p<0.001). The procedure was successful in all the cases. Only one case died. Post -ballooning aortic incompetence was moderate in 2 cases (5.4%) and severe in only one case (2.7%).Conclusions: Balloon aortic valvuloplasty is an effective and safe technique for relieving severe aortic valvular stenosis with acceptable morbidity and minimal mortality, particularly with the new catheter and balloon technology.

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Radhakrishna, Uppala, Samet Albayrak, Zeynep Alpay-Savasan, Amna Zeb, Onur Turkoglu, Paul Sobolewski et Ray O. Bahado-Singh. « Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS) ». PLOS ONE 11, n^o 5 (6 mai 2016) : e0154010. http://dx.doi.org/10.1371/journal.pone.0154010.

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Kuźma, Łukasz, Jolanta Małyszko, Hanna Bachórzewska-Gajewska, Marta Maria Niwińska, Anna Kurasz, Małgorzata Zalewska-Adamiec, Marcin Kożuch et Sławomir Dobrzycki. « Impact of chronic kidney disease on long-term outcome of patients with valvular heart defects ». International Urology and Nephrology 52, n^o 11 (14 juillet 2020) : 2161–70. http://dx.doi.org/10.1007/s11255-020-02561-4.

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Abstract Introduction Valvular heart diseases (VHD) are becoming a significant problem in the Polish population. Coexistence of chronic kidney disease (CKD) in patients with VHD increases the risk of death and affects further therapeutic strategy. Aim Analysis impact of CKD on long-term prognosis in patients with VHD. Material and methods The inclusion criteria were met by 1025 patients with moderate and severe VHD. Mean observation time was 2528 ± 1454 days. Results The average age of the studied population was 66.75 (SD = 10.34), male gender was dominant 56% (N = 579). Severe aortic valve stenosis (AVS) occurred in 28.2%, severe mitral valve insufficiency (MVI) in 20%. CKD occurred in 37.1% (N = 380) patients mostly with mitral stenosis (50%, N = 16) and those with severe MVI (44.8%, N = 94). During the observational period, 52.7% (N = 540) deaths were noted. Increased risk of mortality was associated mostly with age (OR: 1.02, 95% CI: 1.00–1.03, p < 0.001), creatinine (OR:1.27, 95% CI: 1.12–1.43, p < 0.001), CKD (OR: 1.30, 95% CI: 1.17–1.44, p < 0.001), reduced ejection fraction (EF) (OR: 0.98, 95% CI: 0.97–0.99, p = 0.01) and coexisting of AVS (OR: 1.19, 95% CI: 1.04–1.35, p = 0.01). Conclusions Mitral valve defects more often than aortic valve defects coexist with chronic kidney disease. Regardless of the stage, chronic kidney disease is an additional factor affecting the prognosis in patients with heart defects. Factors increasing the risk of death were age, creatinine concentration and reduced EF. The monitoring of renal function in patients with VHD should be crucial as well as the implementation of treatment at an early stage.

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Restovic, Gabriela, Joan Sagarra, Laura Sampietro-Colom et Marta Sitges. « OP104 Moving Forward Hospital-Based Health Technology Assessment : Public Procurement Of Innovation ». International Journal of Technology Assessment in Health Care 34, S1 (2018) : 38–39. http://dx.doi.org/10.1017/s0266462318001344.

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Introduction:Innovation procurement is a key enabler to improve the quality and efficiency of public healthcare services by driving innovation from demand side to meet concrete public healthcare provider needs. Catalan Health Services (CatSalut) aims to optimize healthcare services through innovative solutions that encompass both innovative technologies and new processes of care. Answering this aim, the Hospital Clinic of Barcelona (HCB) is participating in an Innovative Pilot Program to optimize the efficiency in the management of Aortic Valve Stenosis (AVS) using an adaptation of the methods and knowledge from hospital-based health technology assessment (HB-HTA).Methods:The first step was to identify unmet needs, main bottlenecks and problems in the comprehensive management of aortic valve stenosis (AVS) (from primary care to hospital discharge). Innovative technologies, solutions and health care organizations were proactively scanned through literature review and professional expertise. Lists of solutions were proposed through an inclusive stakeholder participation process.Results:A new healthcare model was proposed to be evaluated in the next three years based on an integral, transversal and multidisciplinary management of AVS (named MITMEVA). For each new proposed solution, the management, work streams, expected impact and key performance indicators (based on stakeholder information demands) were defined. To test the potential of the proposal, a theoretical modeling of the economic, clinical and process impacts of implementation was performed based on available scientific evidence, local professional and economic data. This analysis shows more quality-adjusted life years, fewer adverse effects and lower cost with the new proposed model.Conclusions:HB-HTA usually recommends for/against investments. In the era of value based procurement, HB-HTA can also help in developing a Public Procurement of innovative solutions (PPI) project and in testing proactively its potential impact in healthcare, which will be later tested in real life. Therefore, adapting HB-HTA to hospital innovative procurement is another way for health technology assessment to push for the implementation and testing of high value innovative technologies.

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Valls-Comamala, Victòria, Carla Fernandez-Barceló, Marc Trilla, Barbara Vidal, Marta Sitges et Laura Sampietro-Colom. « PP53 Applying The VALIDATE Approach To Frame The Assessment Of Integrated Care Management In Aortic Valve Stenosis ». International Journal of Technology Assessment in Health Care 38, S1 (décembre 2022) : S58. http://dx.doi.org/10.1017/s0266462322001921.

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IntroductionThe assessment of current technologies needs a more holistic approach to obtain accurate recommendations for decision-making. The VALues In Doing Assessments of health TEchnologies (VALIDATE) methodology considers that facts and values from all stakeholders need to be included in the scoping of an assessment to gather the comprehensive information needed for unbiased decision-making. This report aimed to explore how to properly assess the integrated care of patients with aortic valve stenosis (AVS) using the VALIDATE approach.MethodsA literature review was conducted, and 11 semi-structured interviews were performed with various hospital-based healthcare professionals (cardiac surgeon, clinical cardiologist, interventional cardiologist, anesthetist, process coordinator nurse, and others) and patients. Content analysis was used for data analysis and integration.ResultsThe literature review showed that the cardiology and cardiac surgery perspectives were dominant in 90 percent of the articles and present in the remaining ten percent. The perspectives of other specialties (anesthesiology, primary care, and psychology) were included in three percent of the articles and patient perspectives were included in nine percent. Interviewing and considering the perspectives of the different stakeholders involved in the care pathway identified the following indicators that should be included in the assessment care for patients with AVS: difficulties associated with late diagnosis of AVS; the need to incorporate a multidisciplinary approach in patient risk assessment; the importance of geriatric evaluations; considering patient (and family and caregiver) preferences for type of treatment; the importance of following up pharmaceutical treatment and palliative care; use of telemonitoring; and digital exclusion of patients with respect to the use of apps for prehabilitation and rehabilitation.ConclusionsThe stakeholders interviewed were involved in different steps of the care pathway and had differing needs, some of which were not found in the literature. The indicators suggested for inclusion in the assessment differed according to type of stakeholder and their involvement in the care pathway. Therefore, this case study exemplifies the VALIDATE method and endorses the need for multistakeholder involvement in eliciting values when scoping the assessment of a complex technology.

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Sinitskaya, A. V., A. E. Kostyunin, M. A. Asanov, M. V. Khutornaya, A. O. Poddubnyak et A. V. Ponasenko. « Histopathological parallels in infective endocarditis and degenerative defects of native heart valves and their bioprostheses ». Siberian Journal of Clinical and Experimental Medicine 39, n^o 2 (10 juillet 2024) : 166–74. http://dx.doi.org/10.29001/2073-8552-2024-39-2-166-174.

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Background. Detailed study of the histopathological events and mechanisms accompanying the infectious process in native heart valves and their biological prostheses is very important due to the variability of clinical manifestation of infective endocarditis (IE).Aim: To study cellular infiltration of aortic heart valves (AVs) and bioprosthetic heart valves (BPs) affected by infection, as well as to search for common patterns or differences of native and BPs characterized by degenerative changes in the leaflet apparatus.Material and Methods. We studied the leaflets of AVs affected IE (n = 10) or calcific aortic stenosis (CAS) (n = 11), as well as the leaflets of BPs affected by IE (n = 5) or structural valve degeneration (SVD) (n = 10) and removed from the mitral position during re-prosthetics surgery. Histological sections were prepared using a cryostat microtome. Cell typing was performed by staining with antibodies to the CD45, CD68 CD3, CD19, myeloperoxidase (MPO) and CD31 markers using immunohistochemical analysis. Bacteria were visualized by Gram staining of histological sections. The expression of MPO in the studied samples was determined by Western blotting.Results. Colonies of gram-positive cocci and gram-negative rod-shaped bacteria were registered into native AKs affected by IE. BPs affected by SVD are characterized by the presence of mixed colonies of gram-positive cocci and gram-negative rod-shaped bacteria. Immunophenotyping demonstrated leukocyte infiltration (CD45+) in all studied heart valves. AVs and BPs with infectious lesions and BPs affected by SVD were characterized by inflammatory infiltrates included macrophages (CD68+), neutrophils (MPO+) and single T-lymphocytes (CD3+). In calcified AVs, we found no neutrophils; the clusters of immune cells were represented by macrophages and single T-lymphocytes. In both groups of AVs, single cells positive for the vascular endothelial marker CD31 were noted in the fibrous layer. The highest expression of MPO was observed in AVs affected by IE in comparison to other studied valves.Conclusion. AVs affected by infection compared to native heart valves affected by CAS are characterized by aggressive infiltration by neutrophils. Neutrophils and bacterial agents were also detected in BPs regardless of the diagnosed IE. These results indicate the involvement of bacterial invasion in the development of SVD of the biological element of BPs and indicate the necessarily for a detailed study of this phenomenon.

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Takahashi, Koji, Tomoyuki Yamamoto et Kohji Shirai. « Reasons for the Decline of Cardio-Ankle Vascular Index (CAVI) in Aortic Valve Stenosis (AVS) [Letter] ». Vascular Health and Risk Management Volume 18 (décembre 2022) : 887–88. http://dx.doi.org/10.2147/vhrm.s399737.

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Yasuhara, Jun, Karlee Schultz, Amee M. Bigelow et Vidu Garg. « Congenital aortic valve stenosis : from pathophysiology to molecular genetics and the need for novel therapeutics ». Frontiers in Cardiovascular Medicine 10 (28 avril 2023). http://dx.doi.org/10.3389/fcvm.2023.1142707.

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Congenital aortic valve stenosis (AVS) is one of the most common valve anomalies and accounts for 3%–6% of cardiac malformations. As congenital AVS is often progressive, many patients, both children and adults, require transcatheter or surgical intervention throughout their lives. While the mechanisms of degenerative aortic valve disease in the adult population are partially described, the pathophysiology of adult AVS is different from congenital AVS in children as epigenetic and environmental risk factors play a significant role in manifestations of aortic valve disease in adults. Despite increased understanding of genetic basis of congenital aortic valve disease such as bicuspid aortic valve, the etiology and underlying mechanisms of congenital AVS in infants and children remain unknown. Herein, we review the pathophysiology of congenitally stenotic aortic valves and their natural history and disease course along with current management strategies. With the rapid expansion of knowledge of genetic origins of congenital heart defects, we also summarize the literature on the genetic contributors to congenital AVS. Further, this increased molecular understanding has led to the expansion of animal models with congenital aortic valve anomalies. Finally, we discuss the potential to develop novel therapeutics for congenital AVS that expand on integration of these molecular and genetic advances.

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Wen, Dezhong, Li Hu, Jianggui Shan, Hengyuan Zhang, Liuhua Hu, Ancai Yuan, Jun Pu et Song Xue. « Mechanical injury accentuates lipid deposition in ApoE–/– mice and advance aortic valve stenosis : A novel modified aortic valve stenosis model ». Frontiers in Cardiovascular Medicine 10 (2 février 2023). http://dx.doi.org/10.3389/fcvm.2023.1119746.

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BackgroundCurrent mouse models still have limitations in studying aortic valve stenosis (AVS). A suitable animal model bearing a close resemblance to the pathophysiological processes of humans needs to be developed. Here, we combined two risk factors to create a mouse model that mimics the pathological features of human AVS.Methods and resultsWe combined WI and hyperlipidemia in ApoE–/– mice to explore the synergistic effect on the stenosis of the aortic valve. Transthoracic echocardiography revealed progressively increased peak velocity with age in ApoE–/– mice to velocities above C57 mice when fed a high-fat diet after wire injury. Moreover, ApoE–/– mice demonstrated lower cusp separation and lower aortic valve area after 8 weeks vs. C57 mice. Gross morphology and MRI showed advanced thickening, sclerosis aortic valve, narrowing of the orifice area, and micro-CT showed obvious calcification in the aortic valves in the hyperlipidemia group after wire injury. Histopathology studies showed thickening and fibrosis of aortic valve leaflets in the hyperlipidemia group after wire injury. Notably, lipid deposition was observed in ApoE–/– mice 8 weeks after wire injury, accompanied by overexpressed apoB and apoA proteins. After wire injury, the hyperlipidemia group exhibited augmented inflammation, ROS production, and apoptosis in the leaflets. Moreover, the combination group exhibited advanced fibro-calcific aortic valves after wire injury.ConclusionOverall, we present the synergistic effect of wire injury and hyperlipidemia on lipoproteins deposition in the development of AVS in ApoE–/– mice, this model bear close resemblance to human AVS pathology.

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Cayer, Lucien G. J., Arun Surendran, Tobias Karakach, Harold M. Aukema et Amir Ravandi. « Valvular Prostaglandins Are Elevated in Severe Human Aortic Valve Stenosis ». Arteriosclerosis, Thrombosis, and Vascular Biology, 15 février 2024. http://dx.doi.org/10.1161/atvbaha.123.320001.

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BACKGROUND: Aortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibrocalcific remodeling of the aortic valve (AV), which impairs function and can ultimately lead to heart failure. Due to gaps in our understanding of the underlying mechanisms of AVS, there are no pharmacological treatments or dietary interventions known to slow AVS progression. Recent studies have begun to suggest oxylipins—a class of bioactive lipids—may be dysregulated in the valves of patients with AVS. METHODS: We utilized high-performance liquid chromatography–tandem mass spectrometry to conduct a targeted oxylipin analysis on human AV tissue and plasma from a cohort of 110 patients undergoing AV surgery. RESULTS: We identified 36 oxylipins in human AV tissue with all showing significant increase in patients with severe AVS. A multivariate model including patient characteristics and valvular oxylipins identified the arachidonic acid-COX (cyclooxygenase) pathway–derived prostanoids to be the most associated with AVS severity. Plasma oxylipin levels were measured in a subset of AV surgery patients and compared with a control group of healthy participants, showing distinct oxylipin profiles between control and disease. CONCLUSIONS: Our comprehensive analysis of oxylipins in the human AV identified the inflammatory and osteogenic regulating prostanoids to be positively correlated with AVS severity. This elucidation of prostanoid dysregulation warrants further research into COX inhibition to mitigate AVS.

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Goody, P. R., D. Christmann, M. R. Hosen, D. Nehl, D. Goody, S. T. Niepmann, A. Zietzer et al. « The role of noncoding RNAs during aortic valve stenosis ». European Heart Journal 41, Supplement_2 (1 novembre 2020). http://dx.doi.org/10.1093/ehjci/ehaa946.1870.

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Abstract Background Aortic valve stenosis (AVS) is the most common valve disease worldwide. Thought to be a purely degenerative disease, it is now clear that shear stress/endothelial dysfunction, lipid deposition and inflammation lead to calcification and stenosis of the valve. There is evidence, that extracellular vesicles (EVs) are actively involved in calcification processes. Practically all cells, including endothelial cells, can generate EVs, which can be shed into the blood stream and into the interstitial space. EVs contain lipids, proteins and nucleic acids, including noncoding RNAs (ncRNAs). EVs can be taken up by acceptor cells and their cargo, especially the ncRNA content, can change the phenotype of these cells. NcRNAs have been shown to have protective and damaging properties in AVS, which can lead to disease progression. EVs are actively involved in atherosclerosis and vascular calcification, but their role during AVS formation remains largely unknown. Purpose We hypothesize, that EV-derived ncRNAs play a crucial role during calcification of the aortic valve through regulation of endothelial to mesenchymal transition (EndMT) and calcification of valvular interstitial cells. Methods and results In initial screening experiments, we investigated ncRNA (micro RNA, miRNA and long noncoding RNA, lncRNA) content in aortic valve tissue from explanted human aortic valves from patients undergoing surgical aortic valve replacement. There is a differential expression of miRNAs and lncRNAs in aortic valve tissue from patients with AVS and patients without AVS. We could also show a differential packaging of ncRNAs into EVs generated from patient aortic valve tissues. Furthermore, ncRNA expression in aortic valve tissue is altered in a “wire-injury” mouse model of AVS. We can demonstrate in vitro that EVs and their content can be transferred from valvular endothelial cells (VECs) to valvular interstitial cells (VICs) and vice versa. Additionally, we have established an isolation method of VECs and VICs from human samples. To identify ncRNAs involved in EndMT, we are investigating the effect of laminar and pulsatile flow on the expression of ncRNAs in vitro. We can demonstrate that different flow patterns lead to a vast change in ncRNA expression in primary VECs. Downstream effects of identified ncRNAs are currently under investigation in our in vitro calcification and EndMT models. Transfection of VICs with miRNA mimics and inhibitors and lentiviral transduction of our identified targets lead to an altered calcification potential of valve cells. Conclusion The analysis of the cell type specific expression of ncRNAs and the intercellular communication via EVs will greatly help our understanding of the pathomechanisms leading to valvular calcification. Pathway analysis will generate new targets that could be used to develop therapeutics to ameliorate disease progression. EV-based miRNA mimics and inhibitors could be used to treat valvular calcification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft, TRR259; Else-Kröner-Fresenius

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Winnicki, Anna, James Gadd, Vahagn A. Ohanyan, Gilbert Hernandez, Yang Wang, Molly Enrick, Hannah McKillen et al. « Abstract 14024 : Role of Endothelial CXCR4 on the Development of Aortic Valve Stenosis ». Circulation 146, Suppl_1 (8 novembre 2022). http://dx.doi.org/10.1161/circ.146.suppl_1.14024.

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Background. CXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to the Aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS. Methods. We generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4 fl/fl mouse with Tie2-Cre mouse to study the role of endothelial cell CXCR4 in AVS. CXCR4 fl/fl mice with no Tie2-Cre gene present were used as control. Echocardiography was used to assess the aortic valve and cardiac function. Heart samples containing the aortic valve were stained using Alizarin Red for detection of calcification. Masson’s Trichrome staining was used for the detection of fibrosis. Apex samples were stained with wheat germ agglutinin to visualize ventricular hypertrophy. Results. Compared with the control group, the deletion of CXCR4 in endothelial cells led to significantly increased aortic valve peak velocity and aortic valve peak pressure gradient, and decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy evidenced by increased left ventricular mass, diastolic and systolic left ventricle posterior wall (LVPW), cardiac myocyte size, and heart weight (HW) to body weight (BW) ratio. Our data also confirmed increased microcalcifications, interstitial fibrosis, and thickened valvular leaflets of the EC CXCR4 KO mice. Conclusions. We found that the deletion of CXCR4 in endothelial cells leads to aortic valve stenosis and left ventricular hypertrophy. This indicates endothelial cell CXCR4 plays a protective role against AVS, and EC CXCR4 KO mice can be used as a novel model for AVS study.

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Billig, H., J. Schmitt, L. Singer, F. Schildberg, P. R. Goody, W. Vogel, S. Perner, G. Nickenig et S. Zimmer. « The impact of postmenopausal osteoporosis on aortic valve stenosis in an animal model ». European Heart Journal 44, Supplement_2 (novembre 2023). http://dx.doi.org/10.1093/eurheartj/ehad655.3205.

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Abstract Background Aortic valve stenosis (AVS) is the most prevalent heart valve disease worldwide and mainly affects the elderly. In observational clinical studies, postmenopausal osteoporosis, which affects 30 % of all women, is associated with increased aortic valve calcification and stenosis. However, there are no pathomechanistic investigations that link these diseases. In this study, we analyzed the impact of postmenopausal osteoporosis in ovariectomized C57BL6/J mice on the occurrence and progression of wire injury-induced aortic valve stenosis. Methods To induce postmenopausal osteoporosis, we performed bilateral ovariectomy (OVX) or sham operation in C57BL6/J mice. Successful OVX was confirmed by measuring the uterine weight. To distinguish the impact of estrogen deprivation from osteoporosis effects, 100 µg of the bisphosphonate zoledronic acid (ZA) or vehicle were applied i.p. weekly. Bone density was assessed through histological and µCT-analysis of the distal femur. 14 days after ovariectomy, AVS (or sham-procedure) was induced through a standardized, echocardiography-controlled injury of the aortic valve with a spring wire. Primary endpoint was the increase of peak velocity 2, 4 and 6 weeks after AVS-procedure. 8 weeks after OVX, mice were sacrificed and organs were harvested for further analysis (Fig. 1A). Results Bone mineral density and relative bone volume was significantly reduced 8 weeks after OVX. ZA led to a significant increase in bone mineral density, trabecular thickness and relative bone volume in comparison to the sham/vehicle and OVX/vehicle-groups (Fig. 1B-C). AVS was successfully induced, as shown by a significant increase in peak velocity (PV; Fig. 2A-B) 2, 4 and 6 weeks after wire injury. PV and mean pressure gradient (MPG) showed no difference between OVX- or Sham-operated mice (Fig. 2A). ZA did not significantly affect PV or MPG after AVS-procedure (Fig. 2B). Histological analysis revealed significantly greater cusp area in mice with AVS, but no difference for OVX- or ZA-groups (Fig. 2C). Picrosirius red staining showed a significantly decreased relative and absolute collagen content in aortic valves derived from mice with AVS, but no difference between OVX- or ZA-groups was detectable. Immature/degraded collagen was increased in mice with AVS. Conclusion Estrogen depletion and reduction in bone mineral density did affect AVS development in C57BL6/J mice. Application of ZA was effective in preventing bone loss, but did not change AVS-severity. Further histological analysis of the aortic valves could reveal potential differences in cardiovascular osteoclast- and immune cell-infiltration.Figure 1Figure 2

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Rao, P. Syamasundar. « Pictorial rendition of author’s observations on balloon valvuloplasty/angioplasty procedures : Aortic stenosis ». Brain & ; Heart, 25 juillet 2024, 2914. http://dx.doi.org/10.36922/bh.2914.

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Balloon aortic valvuloplasty (BAV) effectively decreases peak pressure gradients through the aortic valve both at the time of the procedure and during follow-up. This paper presents the author’s observations on the utility of BAV in treating congenital aortic valve stenosis (AVS). Previous work by the author noted intermediate-term restenosis and late-onset aortic insufficiency (AI). Factors contributing to restenosis include age under 3 years and post-balloon residual aortic valve gradients exceeding 30 mmHg. Repeat balloon valvuloplasty has been found to address restenosis effectively. However, the onset of AI at late follow-up is a significant disadvantage of BAV. Despite this, BAV is currently considered a beneficial treatment option for managing AVS in children, adolescents, and young adults. In contrast, seniors with calcific AVS do not experience relief from obstruction with BAV and are candidates for aortic valve replacement through transcatheter methodology, a procedure not reviewed in this paper. BAV provides relief of obstruction across the aortic valve and functions as an alternative to surgical intervention. Consequently, BAV is considered a preferred choice in addressing aortic stenosis in the pediatric patient.

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Plunde, O., P. Sarajlic, A. Franco-Cereceda et M. Back. « Atherosclerosis associated pathways are upregulated in stenotic aortic valves from patients with severe concomitant coronary artery disease ». European Heart Journal 42, Supplement_1 (1 octobre 2021). http://dx.doi.org/10.1093/eurheartj/ehab724.1561.

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Abstract Aortic valve stenosis (AVS) share pathobiology and risk factors with atherosclerosis. However, medical treatment effective against atherosclerosis lack ability to halt the progression of AVS. The aims of this study were to (i) determine the prevalence of coronary artery disease (CAD) in surgical AVS patients and (ii) to establish predictors of CAD in AVS patients and (iii) to identify differential aortic valve transcriptomic profiles depending on concomitant CAD. The study cohort consisted of 256 consecutive AVS patients with surgically verified tricuspid aortic valves, of which 74 aortic valves were collected. CAD defined as coronary artery stenosis requiring concomitant bypass surgery or previous acute coronary syndrome or percutaneous coronary intervention Transcriptomic data were obtained from microarray analysis of tissues from three different stages of AVS process (healthy, intermediate, and calcified tissue). All comparisons were sex and tissue adjusted. Non-coding probes were removed and a variance filter was applied prior to analysis which yielded 5121 genes. The prevalence of CAD in AVS was 49%. A logistic regression model revealed male sex, claudication, diabetes and current smoking as significant predictors of CAD when age, sex, peak transaortic velocity, hsCRP, eGFR and BMI were held constant. 28 genes were significantly (q<0.05) differentially expressed when aortic valves from patients with (n=43) and without (n=31) CAD were compared. A comparison of patients with concomitant multi vessel disease (2–3 affected vessel territories, n=20) and patients without CAD or single vessel disease (n=54) revealed 189 significantly expressed genes and an optimal visual separation on heatmap (Figure 2). Active-subnetwork-oriented-enrichment analysis identified upregulated aortic valve atherosclerosis associated pathways in multi vessel disease patients related to reactive oxygen species and cytokine signaling. This study provides a novel observation of differential aortic valve gene expression profile depending on concomitant severe CAD. The results revealed that patients with concomitant severe CAD exhibited underlying atherosclerosis-related mechanisms to their aortic valve disease. Therefore, future precision medicine against AVS may be facilitated by assessing concomitant CAD. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Karolinska Institute - Clinical Science Training ProgrammeSwedish Heart Lung Foundation Predictors of concomitant CADDEGs in AVs stratified on severe CAD

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