Search Results (8)

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function, and their interplay have accumulated, resulting in advanced knowledge on the complex functional characteristics of the aortic valve (AV) and root. This has shifted our vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved, with a similar shift towards treatments options that are more hemodynamically centered, such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress-related stimuli. Many of these physiological and hemodynamical processes are under-acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision making. Full article

Background: Early diagnosis of significant valvular heart disease (VHD) enables appropriate implementation of the best therapeutic strategy and follow-up. Cardiac auscultation remains suboptimal in early detection of VHD. The aim of this study was to evaluate the utility of point-of-care ultrasound (POCUS) for early detection of VHD and its severity. Methods: All consecutive patients with VHD who did not have a standard echocardiogram prior to first outpatient cardiology consultation underwent history and physical examination followed by POCUS study by an experienced physician in a general cardiology clinic from June 2017 to August 2022 at our institution. Subsequent standard transthoracic echocardiography (sTTE) was performed as the gold standard. Comparison was performed between POCUS and sTTE for the presence and severity of VHD. sTTE was performed by registered cardiac sonographers and interpreted by another cardiologist blinded to the POCUS results. Results: A total of 77 patients were studied (ge 72 ± 11 years, 58.4% males). A total of 89 significant valvular abnormalities were diagnosed. There were 39 (43.8%) cases of regurgitant VHD, 16 (18.0%) of stenotic VHD and 34 (38.2%) had evaluation for prosthetic valve function. The sensitivity (90.9%; 82.4%; 83.3%; 100%) and specificity (100%; 96.7%; 100%; 100%) were high for detecting ≥ moderate aortic regurgitation (AR), mitral regurgitation (MR), aortic stenosis (AS) and prosthetic valvular abnormality, respectively. The weighted κ coefficient between POCUS and sTTE for the assessment of ≥ moderate MR, AR and AS was 0.81 (95% CI, 0.65–0.97), 0.94 (95% CI, 0.84–1.00) and 0.88 (95% CI, 0.76–1.0), respectively, indicating excellent agreement. Conclusions: POCUS can identify patients with significant VHD and may serve as a powerful screening tool for early detection of significant VHD in the outpatient clinical practice with downstream impact on clinical management of significant VHD. Full article

Aortic valve stenosis (AS) is a common heart valve disease in the elderly population, and its pathogenesis remains an interesting area of research. The degeneration of the aortic valve leaflets gradually progresses to valve sclerosis. The advanced phase is marked by the presence of extracellular fibrosis and calcification. Turbulent, accelerated blood flow generated by the stenotic valve causes excessive damage to the aortic wall. Elevated shear stress due to AS leads to the degradation of high-molecular weight multimers of von Willebrand factor, which may involve bleeding in the mucosal tissues. Conversely, elevated shear stress has been associated with the release of thrombin and the activation of platelets, even in individuals with acquired von Willebrand syndrome. Moreover, turbulent blood flow in the aorta may activate the endothelium and promote platelet adhesion and activation on the aortic valve surface. Platelets release a wide range of mediators, including lysophosphatidic acid, which have pro-osteogenic effects in AS. All of these interactions result in blood coagulation, fibrinolysis, and the hemostatic process. This review summarizes the current knowledge on high shear stress-induced hemostatic disorders, the influence of AS on platelets and antiplatelet therapy. Full article

The calcification of the aortic valve causes increased leaflet stiffness and leads to the development and progression of stenotic aortic valve disease. However, the molecular and cellular mechanisms underlying stenotic calcification remain poorly understood. Herein, we examined the gene expression associated with valve calcification and the progression of calcific aortic valve stenosis. We downloaded two publicly available gene expression profiles (GSE83453 and GSE51472) from NCBI-Gene Expression Omnibus database for the combined analysis of samples from human aortic stenosis and normal aortic valve tissue. After identifying the differentially expressed genes (DEGs) using the GEO2R online tool, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We also analyzed the protein–protein interactions (PPIs) of the DEGs using the NetworkAnalyst online tool. We identified 4603 upregulated and 6272 downregulated DEGs, which were enriched in the positive regulation of cell adhesion, leukocyte-mediated immunity, response to hormones, cytokine signaling in the immune system, lymphocyte activation, and growth hormone receptor signaling. PPI network analysis identified 10 hub genes: VCAM1, FHL2, RUNX1, TNFSF10, PLAU, SPOCK1, CD74, SIPA1L2, TRIB1, and CXCL12. Through bioinformatic analysis, we identified potential biomarkers and therapeutic targets for aortic stenosis, providing a theoretical basis for future studies. Full article

Purinergic signaling is associated with a vast spectrum of physiological processes, including cardiovascular system function and, in particular, its pathological calcifications, such as aortic valve stenosis. Aortic valve stenosis (AS) is a degenerative disease for which there is no cure other than surgical replacement of the affected valve. Purinergic signaling is known to be involved in the pathologic osteogenic differentiation of valve interstitial cells (VIC) into osteoblast-like cells, which underlies the pathogenesis of AS. ATP, its metabolites and related nucleotides also act as signaling molecules in normal osteogenic differentiation, which is observed in pro-osteoblasts and leads to bone tissue development. We show that stenotic and non-stenotic valve interstitial cells significantly differ from each other, especially under osteogenic stimuli. In osteogenic conditions, the expression of the ecto-nucleotidases ENTPD1 and ENPP1, as well as ADORA2b, is increased in AS VICs compared to normal VICs. In addition, AS VICs after osteogenic stimulation look more similar to osteoblasts than non-stenotic VICs in terms of purinergic signaling, which suggests the stronger osteogenic differentiation potential of AS VICs. Thus, purinergic signaling is impaired in stenotic aortic valves and might be used as a potential target in the search for an anti-calcification therapy. Full article

Valvular heart disease is a rapidly growing cause of global cardiovascular morbidity and mortality with diverse and evolving geographic distribution. The prevalence of rheumatic heart disease, the most common valvular heart disease (affecting approximately 41 million people), has been rising in developing nations, likely due to the expansion of the young adult population and the decrease in premature mortality that has resulted from improved access to antibiotics, microbiological testing, and echocardiography. Rheumatic heart disease has also been rising among the impoverished and, often, indigenous populations of developed nations, spurring public health initiatives that are aimed at alleviating healthcare disparities. Aortic valve stenotic disease is the most commonly occurring valvular pathology in developed nations (afflicting 9 million people worldwide) and its prevalence has been increasing with population aging and the increased prevalence of atherosclerosis. Aortic regurgitation is associated with diastolic, but not systolic, hypertension and it has likewise seen a rise in the developed world. Mitral regurgitation affects 24 million people worldwide, with great variability between and among nations. Primary mitral regurgitation arises as a consequence of myxomatous degeneration and mitral valve prolapse, which is largely due to genetic predispositions, while secondary mitral regurgitation accounts for 65% of cases and arises secondary to dilation and heart failure. Tricuspid regurgitation has become more prevalent in developed nations due to the increased usage of intracardiac pacemakers. Infective endocarditis prevalence has also grown in developed nations, likely due to population aging and the increased utilization of transcatheter valve replacement and prosthetic valves as interventions against the previously discussed valvular pathologies. Full article

(1) Background. Bicuspid aortic valve (BAV) is associated with genetic defects (NOTCH 1, GATA 5) and aortopathy. Differences in the flow patterns and a genetic predisposition could also affect coronary arteries. The objective was to assess the coronary artery calcium score (CACS) and coronary artery disease (CAD) burden by coronary computed tomography angiography (CTA) in patients with BAV stenosis, as compared to stenotic tricuspid aortic valves (TAV). (2) Methods. A retrospective case–control study. A total of 47 patients with BAV stenosis (68.9 years ± 12.9, 38.3% females) who underwent CTA were matched with 47 TAV stenosis patients for age, gender, smoking, arterial hypertension, dyslipidemia, diabetes, body-mass-index and chronic kidney disease. (3) Results. The coronary artery calcium score (CACS) was lower in BAV (237.4 vs. 1013.3AU; p < 0.001) than in TAV, and stenosis severity was less (CAD-RAD^TM: p < 0.001). More patients with BAV had CACS zero (27.7% vs. 0%; p < 0.001). The majority (68.1%) of patients with BAV had no or non-obstructive CAD but only 25.5% of TAV (p < 0.001). Obstructive CAD (>50% stenosis) by CTA was more frequently observed in patients with TAV (68.1%; p < 0.001). (4) Conclusions and Relevance. Patients with BAV stenosis have markedly less coronary calcium and less severe coronary stenosis. CTA succeeds to rule out obstructive CAD in the majority of BAV, with adherent implications for TAVR planning. Full article

The formation of superimposed tissue (SIT), a layer on top of the original valve leaflet, has been described in patients with mitral regurgitation as a major contributor to valve thickening and possibly as a result of increased mechanical stresses. However, little is known whether SIT formation also occurs in aortic valve disease. We therefore performed histological analyses to assess SIT formation in aortic valve leaflets (n = 31) from patients with aortic stenosis (n = 17) or aortic regurgitation due to aortic dilatation (n = 14). SIT was observed in both stenotic and regurgitant aortic valves, both on the ventricular and aortic sides, but with significant differences in distribution and composition. Regurgitant aortic valves showed more SIT formation in the free edge, leading to a thicker leaflet at that level, while stenotic aortic valves showed relatively more SIT formation on the aortic side of the body part of the leaflet. SIT appeared to be a highly active area, as determined by large populations of myofibroblasts, with varied extracellular matrix composition (higher collagen content in stenotic valves). Further, the identification of the SIT revealed the presence of foldings of the free edge in the diseased aortic valves. Insights into SIT regulation may further help in understanding the pathophysiology of aortic valve disease and potentially lead to the development of new therapeutic treatments. Full article