Valve Calcification Research Articles

Multimodality assessment of high- vs. low-gradient aortic stenosis using echocardiography and cardiac CT

BackgroundAortic valve area (AVA) using CT-LVOT area (AVACT-LVOT) <1.2 ​cm2 has been shown comparable to echocardiography AVA of <1.0 ​cm2 for severe aortic stenosis (AS). Current study evaluates how AS diagnosis will be affected when we substitute CT-LVOT with echo derived LVOT. MethodsWe retrospectively studied 367 patients who underwent cardiac CTA and echocardiogram for assessment of high- and low-gradient AS (HG-AS and LG-AS). AVACT-LVOT was derived from CT-LVOT area and echo doppler data. Three AVACT-LVOT categories were created (<1.0, 1.0–1.2 and ​> ​1.2 ​cm2). Outcomes were defined as composite of all-cause mortality and/or valve intervention. ResultsMedian echocardiographic profiles were consistent with severe AS across three AVACT-LVOT categories for HG-AS. HG-AS patients with AVACT-LVOT >1.2 ​cm2 had larger median CT-LVOT area (5.06 ​cm2) and AVC (2917AU). Among LG-AS with AVACT-LVOT ​≤1.2 cm2, 57% met echo criteria for low-flow LG-AS and 63% met criteria for severe AS using aortic valve calcium (AVC). Additionally, 45% with AVACT-LVOT >1.2 ​cm2 had larger median CT-LVOT area (5.43 ​cm2) and AVC (2389AU). Patients with AVACT-LVOT >1.2 ​cm2 and high AVC had large body surface area and were mostly characterized as severe with indexed AVA and AVC. Stroke volume index using CT-LVOT reclassified 70% of low-flow, LG-AS as normal flow, LG-AS. Composite outcomes were higher among patients with AVACT-LVOT ≤1.2 ​cm2 (p ​< ​0.01), however, with no superior net reclassification improvement compared to AVAecho <1.0 ​cm2. ConclusionAVACT-LVOT ≤1.2 ​cm2 is a reasonable CT criterion for severe AS. Large LVOT with elevated AVC identified a severe AS phenotype despite an AVACT-LVOT >1.2 ​cm2, best characterized by indexed AVA and AVC.

TCT-278 Impact of Mitral Annular Calcification and Concomitant Mitral Valve Disease on Transcatheter Aortic Valve Replacement Outcomes: A Systematic Review and Meta-Analysis

TCT-278 Impact of Mitral Annular Calcification and Concomitant Mitral Valve Disease on Transcatheter Aortic Valve Replacement Outcomes: A Systematic Review and Meta-Analysis

TCT-625 Staging Classification of Mitral Annular Calcification and Severe Mitral Valve Dysfunction

TCT-625 Staging Classification of Mitral Annular Calcification and Severe Mitral Valve Dysfunction

TCT-687 Prevalence and Characteristics of Aortic Valve Calcification in the General Population

TCT-687 Prevalence and Characteristics of Aortic Valve Calcification in the General Population

CardioVision: A fully automated deep learning package for medical image segmentation and reconstruction generating digital twins for patients with aortic stenosis.

Aortic stenosis (AS) is the most prevalent heart valve disease in western countries that poses a significant public health challenge due to the lack of a medical treatment to prevent valve calcification. Given the aging population demographic, the prevalence of AS is projected to rise, resulting in a progressively significant healthcare and economic burden. While surgical aortic valve replacement (SAVR) has been the gold standard approach, the less invasive transcatheter aortic valve replacement (TAVR) is poised to become the dominant method for high- and medium-risk interventions. Computational simulations using patient-specific models, have opened new research avenues for optimizing emerging devices and predicting clinical outcomes. The traditional techniques of generating digital replicas of patients' aortic root, native valve, and calcification are time-consuming and labor-intensive processes requiring specialized tools and expertise in anatomy. Alternatively, deep learning models, such as the U-Net architecture, have emerged as reliable and fully automated methods for medical image segmentation. Two-dimensional U-Nets have been shown to produce comparable or more accurate results than trained clinicians' manual segmentation while significantly reducing computational costs. In this study, we have developed a fully automatic AI tool capable of reconstructing the digital twin geometry and analyzing the calcification distribution on the aortic valve. The developed automatic segmentation package enables the modeling of patient-specific anatomies, which can then be used to simulate virtual interventional procedures, optimize emerging prosthetic devices, and predict clinical outcomes.

TCT-391 Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis

TCT-391 Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis

Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves.

Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. STATEMENT OF SIGNIFICANCE: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.

TCT-690 Sex Differences in the Prevalence of Aortic Valve Calcification in the General Population

TCT-690 Sex Differences in the Prevalence of Aortic Valve Calcification in the General Population

Tanshinone IIA attenuates valvular interstitial cells' calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress.

Recent studies revealed that endoplasmic reticulum (ER) stress played an emerging role of in valve calcification. Tanshinone IIA (TanIIA) has been a research hotspot in cardiovascular diseases. Previously we found that sodium TanIIA dampened the pathological phenotype transition of valvular interstitial cells (VICs) by affecting ER stress published in Chinese Journal. Here, we test the hypothesis that TanIIA attenuates the pro-osteogenic effects of oxidized low-density lipoprotein (oxLDL) in VICs by reducing induction of ER stress. Patients' aortic valve (AV) was collected, and porcine VICs were cultured for in vitro model. ER stress markers were tested in human leaflets by immunostaining. Immunoblotting were used to test the osteoblastic factors such as Runx2, osteocalcin, and ER stress markers GRP78, CHOP, XBP1, etc. Alkakine phosphate (ALP) activity assay were used to test the activity of ALP kinase. Pro-inflammatory gene expression was detected by polymerase chain reaction. As a result, ER stress markers were elevated in patients' calcified AVs. OxLDL induced osteogenesis and inflammation via promoting ER stress. TanIIA attenuated oxLDL induced ER stress. TanIIA also inhibited theosteoblastic factors and inflammatory cytokine expressions in VICs. In conclusion, our data provide evidence that TanIIA exerts anti-inflammation and anti-osteogenic effects in VICs by attenuating ER stress, and ER stress acts as an important regulator in oxLDL induced VICs' phenotype transition.

Different prognostic significance of coronary artery and aortic valve calcium in patients with chest pain.

Coronary artery calcification (CorCa) identifies high cardiovascular risk in the general population. In this setting, aortic valve calcification (AoCa) showed contradictory results. Our goal has been to assess the prognostic power of CorCa and AoCa in patients with chest pain who underwent an ECG-gated cardiac multidetector CT (cardiac-MDCT). A total of 528 patients without previous known coronary artery disease, with chest pain who underwent a cardiac-MDCT multidetector, were retrospectively recruited. The primary endpoint included death, acute coronary syndrome, stroke, and heart failure. A total of 61 patients (11.6%) had an event during a mean follow-up of almost 6years (5.95 ± 2.98). The most frequent event was acute coronary syndrome (6.4%). Total mortality was 4.5%. Patients with CorCa > 0 had more events than those without CorCa (17.3% versus 4.3%; p < 0.001). Likewise, when only patients without AoCa were considered (n = 118), clinical events were more frequent in those with CorCa (12.7% versus 3.6%; p = 0.004). After excluding patients with coronary artery disease, events were more frequent in those with CorCa (12.6% versus 4.3%; p = 0.004). The higher the Agatston score, the more frequent the events. Patients with AoCa > 0 had more events than those without (16.5% versus 7.3%; p < 0.001), but in patients without CorCa, no difference in events was seen (6.2% versus 3.6%; p = 0.471). A Cox regression analysis showed age, smoking, prior stroke, and CorCa but not AoCa to be independently related to events. In summary, CorCa, but not AoCa, is related to cardiovascular events in patients with chest pain who undergo a cardiac-MDCT. We show that coronary artery calcification, but not aortic valve calcification, detected in a coronary CT scan is tightly related to cardiovascular events. Although this is a message already shown by other groups in the general population, we do believe that this work is unique because it is restricted to patients with chest pain sent to coronary CT. In other words, our work deals with what we face in our routine everyday practice. • The presence and the amount of coronary artery calcification are associated with cardiovascular events in patients with chest pain. • Aortic valve calcification is not associated with cardiovascular events in patients with chest pain.

Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease

Extracellular matrix (ECM) is an active player in cardiovascular calcification (CVC), a major public health issue with an unmet need for effective therapies. Lysyl oxidase (LOX) conditions ECM biomechanical properties; thus, we hypothesized that LOX might impact on mineral deposition in calcific aortic valve disease (CAVD) and atherosclerosis. LOX was upregulated in calcified valves from two cohorts of CAVD patients. Strong LOX immunostaining was detected surrounding calcified foci in calcified human valves and atherosclerotic lesions colocalizing with RUNX2 on valvular interstitial cells (VICs) or vascular smooth muscle cells (VSMCs). Both LOX secretion and organized collagen deposition were enhanced in calcifying VICs exposed to osteogenic media. β-aminopropionitrile (BAPN), an inhibitor of LOX, attenuated collagen deposition and calcification. VICs seeded onto decellularized matrices from BAPN-treated VICs calcified less than cells cultured onto control scaffolds; instead, VICs exposed to conditioned media from cells over-expressing LOX or cultured onto LOX-crosslinked matrices calcified more. Atherosclerosis was induced in WT and transgenic mice that overexpress LOX in VSMC (TgLOXVSMC) by AAV-PCSK9D374Y injection and high-fat feeding. In atherosclerosis-challenged TgLOXVSMC mice both atherosclerosis burden and calcification assessed by near-infrared fluorescence (NIRF) imaging were higher than in WT mice. These animals also exhibited larger calcified areas in atherosclerotic lesions from aortic arches and brachiocephalic arteries. Moreover, LOX transgenesis exacerbated plaque inflammation, and increased VSMC cellularity, the rate of RUNX2-positive cells and both connective tissue content and collagen cross-linking. Our findings highlight the relevance of LOX in CVC and postulate this enzyme as a potential therapeutic target for CVC.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Incremental prognostic value of intensity-weighted regional calcification scoring using contrast CT imaging in TAVR.

Aortic valve calcification scoring plays an important role in predicting outcomes of transcatheter aortic valve replacement (TAVR). However, the impact of relative calcific density and its causal effect on peri-procedural complications due to sub-optimal valve expansion remains limited. This study aims to investigate the prognostic power of quantifying regional calcification in the device landing zone in the context of peri-procedural events and post-procedural complications based on pre-operative contrast computed tomography angiography (CCTA) images. Assess the effect of calcification on post-procedural device expansion and final configuration. We introduce a novel patient invariant topographic scheme for quantifying the location and relative density of landing zone calcification. The calcification was detected on CCTA images based on a recently developed method using automatic minimization of the false positive rate between aortic lumen and calcific segments. Multinomial logistic regression model evaluation and ROC curve analysis showed excellent classification power for predicting paravalvular leakage [area under the curve (AUC) = 0.8; P < 0.001] and balloon pre-dilation (AUC = 0.907; P < 0.001). The model exhibited an acceptable classification ability for left bundle branch block (AUC = 0.748; P < 0.001) and balloon post-dilation (AUC = 0.75; P < 0.001). Notably, all evaluated models were significantly superior to alternative models that did not include intensity-weighted regional volume scoring. TAVR planning based on contrast computed tomography images can benefit from detailed location, quantity, and density contribution of calcific deposits in the device landing zone. Those parameters could be employed to stratify patients who need a more personalized approach during TAVR planning, predict peri-procedural complications, and indicate patients for follow-up monitoring.

Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice.

Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality among elderly people. However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. Male Apoe-/- mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment.

Novel Pharmacological Therapies for the Management of Hyperlipoproteinemia(a).

Lipoprotein(a) [Lp(a)] is a well-established risk factor for cardiovascular disease, predisposing to major cardiovascular events, including coronary heart disease, stroke, aortic valve calcification and abdominal aortic aneurysm. Lp(a) is differentiated from other lipoprotein molecules through apolipoprotein(a), which possesses atherogenic and antithrombolytic properties attributed to its structure. Lp(a) levels are mostly genetically predetermined and influenced by the size of LPA gene variants, with smaller isoforms resulting in a greater synthesis rate of apo(a) and, ultimately, elevated Lp(a) levels. As a result, serum Lp(a) levels may highly vary from extremely low to extremely high. Hyperlipoproteinemia(a) is defined as Lp(a) levels > 30 mg/dL in the US and >50 mg/dL in Europe. Because of its association with CVD, Lp(a) levels should be measured at least once a lifetime in adults. The ultimate goal is to identify individuals with increased risk of CVD and intervene accordingly. Traditional pharmacological interventions like niacin, statins, ezetimibe, aspirin, PCSK-9 inhibitors, mipomersen, estrogens and CETP inhibitors have not yet yielded satisfactory results. The mean Lp(a) reduction, if any, is barely 50% for all agents, with statins increasing Lp(a) levels, whereas a reduction of 80-90% appears to be required to achieve a significant decrease in major cardiovascular events. Novel RNA-interfering agents that specifically target hepatocytes are aimed in this direction. Pelacarsen is an antisense oligonucleotide, while olpasiran, LY3819469 and SLN360 are small interfering RNAs, all conjugated with a N-acetylgalactosamine molecule. Their ultimate objective is to genetically silence LPA, reduce apo(a) production and lower serum Lp(a) levels. Evidence thus so far demonstrates that monthly subcutaneous administration of a single dose yields optimal results with persisting substantial reductions in Lp(a) levels, potentially enhancing CVD risk reduction. The Lp(a) reduction achieved with novel RNA agents may exceed 95%. The results of ongoing and future clinical trials are eagerly anticipated, and it is hoped that guidelines for the tailored management of Lp(a) levels with these novel agents may not be far off.

Predictive value of serum β2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.

Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum β2-microglobulin (β2-MG) levels in predicting the incidence of CVC. β2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood β2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. β2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to β2-MG for MHD patients. Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of β2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. The β2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum β2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a β2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the β2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the β2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum β2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Serum β2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.

MiR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells.

Calcific aortic valve disease (CAVD) is an important cause of disease burden among aging populations. Excessive active endoplasmic reticulum stress (ERS) was demonstrated to promote CAVD. The expression level of miR-199a-5p in patients with CAVD was reported to be downregulated. In this article, we aimed to investigate the function and mechanism of miR-199a-5p in CAVD. The expression level of miR-199a-5p and ERS markers was identified in calcific aortic valve samples and osteogenic induction by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, and western blotting (WB). Alizarin red staining, RT-qPCR, and WB were used for the verification of the function of miR-199a-5p. The dual luciferase reporter assay and rescue experiment were conducted to illuminate the mechanism of miR-199a-5p. In our study, the expression level of miR-199a-5p was significantly decreased in calcified aortic valves and valve interstitial cells' (VICs) osteogenic induction model, accompanying with the upregulation of ERS markers. Overexpression of miR-199a-5p suppressed the osteogenic differentiation of VICs, while downregulation of miR-199a-5p promoted this function. 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6), both of which were pivotal modulators in ERS, were potential targets of miR-199a-5p. miR-199a-5p directly targeted GRP78 and ATF6 to modulate osteoblastic differentiation of VICs. miR-199a-5p inhibits osteogenic differentiation of VICs by regulating ERS via targeting GRP78 and ATF6.

Pattern of cardiovascular diseases at a teaching hospital in Addis Ababa, Ethiopia: An echocardiographic study of 1500 patients.

Cardiovascular diseases (CVD) represent a significant global health problem. They account for nearly one third of deaths worldwide. With improvements in diagnostic modalities, their prevalence in sub-Saharan Africa (SSA) is rising. Disease pattens vary in different regions and communities and the pattern in our setting is not known. Echocardiography is a noninvasive diagnostic tool that essential for structural and hemodynamic assessment of the heart. It stands at the far front for comprehensive evaluation of the heart because of its relative low cost and wide availability. The aim of this study was to assess pattern of CVDs among patients who had echocardiography done at a teaching Hospital in Addis Ababa, Ethiopia. A retrospective review of 1500 echocardiograms of patients referred to the echocardiography laboratory of St. Paul Hospital Millennium Medical College (SPHMMC) for cardiac evaluation from January 1, 2018 to June 30, 2019 was performed. All subjects had standard transthoracic echocardiography performed by cardiologists using General Electric Vivid E9 and E95 machines. Demographic parameters and echocardiographic findings were collected using a structured checklist from the echocardiography register. Descriptive statistics were used to assess the echocardiographic findings. The mean age of subjects was 48.2 (SD of 18.2) and ranged between 14 and 100 years of age. Both males and females were nearly equally distributed with males accounting for 48.3%. Most (77.9%) of the subjects had an abnormal echocardiographic report; only 332 (22.1%) had a normal study. Diastolic dysfunction (DD) (33.4%), valvular heart disease (18.4%), and left ventricular hypertrophy (LVH) (13.7%) were the most common findings in our hospital. Among patients with DD, Grade 1 dysfunction accounted for the majority (79.8%), of which 41% had associated LVH. Pulmonary hypertension (PH), cardiomyopathy and ischemic heart disease were also not uncommon. Abnormal echocardiographic findings are common in patients referred to our hospital for transthoracic echo. The commonest echocardiographic abnormalities were DD, Valvular heart disease (both rheumatic and calcific valves) and LVH.

Relationship between the aortic valve calcification and gradient with carotid stenosis severity and plaque’s morphology in patients with ischemic stroke

Objectives: The relationship between aortic valve calcification (AVC) and aortic valve outflow gradients with carotid artery stenosis (CAS) has been discussed and debated. The present study aims to investigate the relationship between AVC and CAS with the presence and severity of CAS.&#x0D; Methods: In this cross-sectional study, we collected carotid artery (CA) Doppler ultrasonography and echocardiography results from 150 patients hospitalized for ischemic stroke. The case group consisted of 75 patients with an atherosclerotic plaque in the carotid artery with &gt;50% stenosis. Seventy-five patients without atherosclerotic plaques in the carotid artery were included in the control group.&#x0D; Results: AVC and AV peak gradients were significantly higher in the case group compared to the control group (p=0.0001, p=0.015) respectively. In the case group, there was no significant association between AVC and AV peak gradient with the severity of CAS and between AVC and carotid plaque morphology (p=0.88, p=0.14, p=0.089) respectively. The two groups had no significant difference in the rate of aortic regurgitation (AR) (P=0.57).&#x0D; Conclusions: Aortic valve calcification and aortic valve gradients are significantly related to CAS. AVC and aortic valve gradients could be considered risk factors for CAS and stroke. Contrary to this, the severity of gradients and AVC was not directly related to the severity of CAS and its morphology.

Sex discrepancies in pathophysiology, presentation, treatment, and outcomes of severe aortic stenosis.

This review gives an overview of sex-based differences in aortic valve stenosis, spanning from pathophysiological mechanisms and disease progression, clinical presentation, presence of comorbidities, and diagnostic assessment, to treatment and outcomes. In particular, sex-related differences in the degree of aortic valve calcification, the response of the left ventricle to pressure overload, as well as in the referral to procedures, with women being less frequently referred for surgical aortic valve replacement and experiencing longer waiting times for transcatheter procedures, will be discussed. Sex-related differences are also particularly evident in outcomes of patients with severe aortic stenosis undergoing surgical or transcatheter procedures. The apparent sex paradox seen in women undergoing transcatheter aortic valve implantation refers to the phenomenon of women experiencing higher rates of short-term mortality and bleeding events, but demonstrating improved long-term survival as compared to men. Women who undergo surgical aortic valve replacement have generally worse outcomes as compared to men, which is reflected by the inclusion of female sex in surgical risk calculation scores. Hence, a thorough understanding of sex-related differences in aortic valve stenosis is important to provide optimal and personalized patient care.