Materiały źródłowe

• #1 Aortic Stenosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557628/

  Aortic stenosis is a common valvular disorder leading to left ventricular outflow obstruction. […] Etiologies include congenital (bicuspid/unicuspid), calcific, and rheumatic disease. […] A congenitally abnormal valve with superimposed calcification can cause aortic stenosis. […] The bicuspid aortic valve is the most common cause of aortic stenosis in patients less than the age of 70 years in developed countries. […] Rheumatic valve disease is the most common cause in developing countries. […] The commissures of the leaflets fuse to leave a small central orifice. […] Other causes include calcification of the tri-leaflet valve, alkaptonuria, systemic lupus erythematosus, ochronosis, irradiation, homozygous type II lipoproteinemia, and metabolic diseases such as Fabry disease. […] Mineral metabolism disturbances, such as end-stage renal disease, have also been shown to contribute to the calcification of the valve.

• #2 Pathogenesis and pathophysiology of aortic valve stenosis in adults – Polish Archives of Internal Medicine

  https://www.mp.pl/paim/issue/article/1103

  Aortic stenosis (AS) is the most common form of valvular heart disease. AS of degenerative etiology is predominant. It is a persistent disease associated with the activation of 3 processes: lipid accumulation, inflammation, and calcification. Recent studies suggest that valve calcification is an actively regulated process that involves extracellular matrix remodeling, angiogenesis, and inflammation leading to bone formation. Many mechanisms and risk factors involved in the pathogenesis of AS are similar to those observed in atherosclerosis. […] The knowledge of these processes may play a significant role in adequate prevention and therapy of patients with AS, especially at an early stage.

• #3 Current Strategies in the Management of Aortic Stenosis | USC Journal

  https://www.uscjournal.com/articles/final-word-current-strategies-lifetime-management-patients-aortic-valve-stenosis

  Aortic valve stenosis (AS) is the most common form of valvular heart disease in developed countries, with a prevalence that increases exponentially with advancing age. […] Several etiologies, including congenital abnormalities (i.e. bicuspid aortic valve) and rheumatic heart disease, can lead to AS, although degenerative processes directly related to aging are the most common. The progressive fibrosis and calcification of the aortic valve obstruct blood flow from the left ventricle to the ascending aorta during systole. […] Lipid deposition into intima cusps with subsequent oxidation constitutes the primary mechanism of pathogenesis of degenerative AS. This process triggers inflammation and oxidative stress that lead progressively to valve calcification. […] Hypercholesterolemia and high plasma levels of LDL particles are associated with an increase in oxidized LDL deposition in aortic valve leaflets, causing leaflet thickening, macrophage intrusion, and calcification.

• #4 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the conditions mechanistic underpinning has shifted the paradigm to an active disease process. […] The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options. […] The precise pathological mechanism behind the stenosis of the aortic valve remains unresolved. Nonetheless, advancements in technology and research have changed our insight. A once considered passive, degenerative process due to ageing is now understood to be active, similar in its molecular underpinning to atherosclerosis and its associated inflammatory response.

• #5 Pathogenesis of aortic stenosis: not just a matter of wear and tear

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3253493/

  Aortic valve stenosis (AS) is the commonest form of valvular heart disease in the Western world. […] Although risk factors and downstream mediators appear similar for AS and atherosclerosis (older age, male sex, hypertension, smoking, hypercholesterolemia, and diabetes, as many as 50% of patients with AS do not have clinically significant atherosclerosis. […] On the basis both of recent experimental evidence and clinical trials, it appears that atherogenesis is not pivotal to the pathogenesis of AS. […] On the other hand, there is increasing evidence of active involvement of aortic valve fibroblasts with resultant increased production of reactive oxygen species, active pro-inflammatory and pro-fibrotic processes culminating in calcification. […] The renin-angiotensin system has also emerged as a major player in the pathogenesis of AS.

• #6 Pathogenesis and pathophysiology of aortic valve stenosis in adults – Polish Archives of Internal Medicine

  https://www.mp.pl/paim/issue/article/1103

  Aortic stenosis (AS) is the most common form of valvular heart disease. AS of degenerative etiology is predominant. It is a persistent disease associated with the activation of 3 processes: lipid accumulation, inflammation, and calcification. Recent studies suggest that valve calcification is an actively regulated process that involves extracellular matrix remodeling, angiogenesis, and inflammation leading to bone formation. Many mechanisms and risk factors involved in the pathogenesis of AS are similar to those observed in atherosclerosis. […] The knowledge of these processes may play a significant role in adequate prevention and therapy of patients with AS, especially at an early stage.

• #7 Aortic Stenosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557628/

  Aortic stenosis is a common valvular disorder leading to left ventricular outflow obstruction. […] Etiologies include congenital (bicuspid/unicuspid), calcific, and rheumatic disease. […] A congenitally abnormal valve with superimposed calcification can cause aortic stenosis. […] The bicuspid aortic valve is the most common cause of aortic stenosis in patients less than the age of 70 years in developed countries. […] Rheumatic valve disease is the most common cause in developing countries. […] The commissures of the leaflets fuse to leave a small central orifice. […] Other causes include calcification of the tri-leaflet valve, alkaptonuria, systemic lupus erythematosus, ochronosis, irradiation, homozygous type II lipoproteinemia, and metabolic diseases such as Fabry disease. […] Mineral metabolism disturbances, such as end-stage renal disease, have also been shown to contribute to the calcification of the valve.

• #8 Aortic valve stenosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/aortic-stenosis/symptoms-causes/syc-20353139

  Aortic valve stenosis is a type of heart valve disease, also called valvular heart disease. The aortic valve is between the lower left heart chamber and the body’s main artery, called the aorta. In aortic valve stenosis, the valve is narrowed and doesn’t open fully. This reduces or blocks blood flow from the heart to the aorta and to the rest of the body. […] Aortic stenosis is in general a progressive disease. Progressive calcification of the valve results in progressive narrowing and a pressure overload phenomenon in the heart. This can cause thickening of the heart muscle and stiffening. […] Aortic valve stenosis causes include: Heart condition present at birth, called a congenital heart defect. Some children are born with an aortic valve that has only two cusps instead of the usual three. If there are only two cusps, it’s called a bicuspid aortic valve. Rarely, an aortic valve may have one or four cusps.

• #9 Aortic Stenosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557628/

  Aortic stenosis is a common valvular disorder leading to left ventricular outflow obstruction. […] Etiologies include congenital (bicuspid/unicuspid), calcific, and rheumatic disease. […] A congenitally abnormal valve with superimposed calcification can cause aortic stenosis. […] The bicuspid aortic valve is the most common cause of aortic stenosis in patients less than the age of 70 years in developed countries. […] Rheumatic valve disease is the most common cause in developing countries. […] The commissures of the leaflets fuse to leave a small central orifice. […] Other causes include calcification of the tri-leaflet valve, alkaptonuria, systemic lupus erythematosus, ochronosis, irradiation, homozygous type II lipoproteinemia, and metabolic diseases such as Fabry disease. […] Mineral metabolism disturbances, such as end-stage renal disease, have also been shown to contribute to the calcification of the valve.

• #10 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  Knowledge of this active pathophysiology has the potential to change the paradigm of AS management as pathway biomarkers and advanced imaging techniques aim to identify early signs of significant disease and Lp(a) lowering treatments have the potential to slow progression. […] The initiation stage is analogous to that found in atherosclerosis. Initial endothelial insult results in the infiltration of low-density lipoproteins (LDLs) and Lp(a) into the valve, depositing within the fibrosa. […] Following this, reactive oxygen species modify the lipids into oxidised LDLs (OxLDLs). OxLDLs stimulate the extravasation of monocytes into the valve interstitium which consequently differentiate into macrophages. At this stage, the inflammatory cascade initiates; macrophages capture the OxLDLs to form foam cells, enhancing the influx of immune cells through a greater expression of adhesion molecules E-selectin and intercellular adhesion molecule 1, thus perpetuating the cycle.

• #11 Novel Circulating Biomarkers in Aortic Valve Stenosis

  https://www.mdpi.com/1422-0067/26/5/1902

  The underlying pathophysiology of aortic stenosis and factors affecting its clinical progression remain poorly understood. […] Among the biomarkers studied, lipoprotein(a) [Lp(a)] has emerged as the most promising for risk stratification. Elevated Lp(a) levels are often associated with more rapid aortic stenosis progression. This detrimental effect is attributed to its role in promoting valve calcification. […] While once viewed as a passive, age-related process, aortic stenosis is now recognised as an active disease. Its progression can be divided into two phases: initiation and propagation. The initiation phase involves endothelial injury and the subsequent infiltration of Lp(a) and low-density lipoproteins (LDLs) into the valve. […] The subsequent propagation phase is mainly characterised by fibrosis and calcification. Inflammation-activated vascular interstitial cells contribute to fibrosis by secreting matrix metalloproteinases (MMPs) and adopting a myofibroblastic phenotype.

• #12 Pathogenesis of aortic stenosis: not just a matter of wear and tear

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3253493/

  Histopathologic studies have demonstrated that development and progression of calcific AS are based on an active process that shares some similarities with atherosclerosis. […] It has been suggested that aortic valve lesions begin with disruption of valve endothelium predominantly on the aortic side due to high shear stress. […] The presence of macrophages and T-lymphocytes, along with oxidized LDL and apolipoprotein accumulation activate several pro-fibrotic and pro-inflammatory cytokines which may modulate aortic valve remodelling and subsequent calcification. […] Current concepts of the pathogenesis of AS centre histologically on inflammation and lipid deposition, and biochemically on activation of cytokines and matrix metalloproteinases, together with generation of angiotensin II.

• #13 Aortic stenosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Aortic_stenosis_pathophysiology

  The stages of the formation of the calcific aortic stenosis are the following: Endothelial Damage: Endothelial damage is the initial event starting the cascade of events in calcific aortic stenosis. […] Inflammation: Endothelial damage triggers accumulation of lipids (LDL and lipoproteins) that subsequently undergo oxidative changes. […] Fibrosis: Inflammation eventually leads to activation of fibroblasts and remodeling of the extracellular matrix. […] Calcification: Calcification is induced by long standing inflammation and fibrosis. […] Rheumatic aortic stenosis is due to the fusion of the valve commissures and subsequent scarring and calcification. […] Long-standing aortic stenosis exposes the left ventricle to prolonged pressure overload which leads to concentric hypertrophy as a compensatory mechanism to preserve left ventricular function.

• #14 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  Knowledge of this active pathophysiology has the potential to change the paradigm of AS management as pathway biomarkers and advanced imaging techniques aim to identify early signs of significant disease and Lp(a) lowering treatments have the potential to slow progression. […] The initiation stage is analogous to that found in atherosclerosis. Initial endothelial insult results in the infiltration of low-density lipoproteins (LDLs) and Lp(a) into the valve, depositing within the fibrosa. […] Following this, reactive oxygen species modify the lipids into oxidised LDLs (OxLDLs). OxLDLs stimulate the extravasation of monocytes into the valve interstitium which consequently differentiate into macrophages. At this stage, the inflammatory cascade initiates; macrophages capture the OxLDLs to form foam cells, enhancing the influx of immune cells through a greater expression of adhesion molecules E-selectin and intercellular adhesion molecule 1, thus perpetuating the cycle.

• #15 Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA

  https://www.mdpi.com/1422-0067/24/19/14939

  Fibrosis and calcification are the processes that modify the biomechanical properties of valve leaflets. The initial or preclinical lesion is represented by aortic sclerosis, which affects ⅓ of patients over 65 years and half of patients over 85 years. The primum movens is endothelial damage, or “shear stress”, resulting in lipid infiltration, particularly LDL and Lpa. It has been assessed that the levels of apoB, apoE, apoA1, and apo(a) are present in surgically removed stenotic aortic valves. The activation of the inflammatory process causes dysregulation of the eNOS (endothelial nitric oxide synthase) pathway and ROS production. This initiates lipid oxidation with the transformation of Lpa into Ox-LP and LDL into OxLDL. The lipids accumulated in the valve carry enzymes: LpPLA2 transported by LDL and autotaxin (ATX) transported by Lpa. These enzymes produce lysophospholipid derivatives, bioactive lipid compounds. LpPLA2 converts Ox-LP into lysophosphatidylcholine (LysoPC), which causes the activation of the apoptotic process of VICs. In addition, LpPLA2 generates AA (arachidonic acid) that promotes the formation of inflammatory molecules via the cyclooxygenase2 (Cox2) and 5-lipoxygenase (5-LO) pathways. These proinflammatory molecules promote mineralization by increasing the expression of bone morphogenetic proteins 2 and 6 (BMP2 and BMP6).

• #16 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  The propagation phase of CAS is characterised by repeated fibrosis and calcification. Inflammation activated VICs induce fibrosis by the secretion of matrix metalloproteinases through a myofibroblastic phenotype. […] This scarred tissue acts as a nidus for calcification in which inflammation-induced apoptosis of VICs leads to diffuse microcalcification through the release of apoptotic bodies. […] As the disease progresses, stiffening of the valve prompts further apoptosis, resulting in the calcific mechanisms superseding the immunological pathway in propagating CAS. […] The macroscopic manifestations of CAS, as a result of cellular pathological processes, affect the aortic valve and surrounding myocardium. Initially, valve disease is difficult to detect. […] Within 7 years, 10% of these patients would progress to CAS, distinguished by restricted valve motion and haemodynamic obstruction.

• #17 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  The propagation phase of CAS is characterised by repeated fibrosis and calcification. Inflammation activated VICs induce fibrosis by the secretion of matrix metalloproteinases through a myofibroblastic phenotype. […] This scarred tissue acts as a nidus for calcification in which inflammation-induced apoptosis of VICs leads to diffuse microcalcification through the release of apoptotic bodies. […] As the disease progresses, stiffening of the valve prompts further apoptosis, resulting in the calcific mechanisms superseding the immunological pathway in propagating CAS. […] The macroscopic manifestations of CAS, as a result of cellular pathological processes, affect the aortic valve and surrounding myocardium. Initially, valve disease is difficult to detect. […] Within 7 years, 10% of these patients would progress to CAS, distinguished by restricted valve motion and haemodynamic obstruction.

• #18 Pathogenesis of aortic stenosis: not just a matter of wear and tear

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3253493/

  The process of calcification (and sometimes ossification) of aortic valve leaflets resembles that associated with atheroma formation. […] It has also been shown that the calcification process of aortic valves may also be regulated by receptor activator of nuclear factor B, its ligand (RANK, and RANKL), and the soluble receptor osteoprotegerin (OPG). […] A critical question which arises is whether the pathogenesis of AS is fundamentally related to dysfunction of the valve endothelium. […] The main luminal implication of these studies was that the stenotic aortic valve constitutes a pro-aggregatory milieu: – the clinical consequences of a loss of valve anti-aggregatory function must be considered together with platelet hyperaggregability and platelet resistance to NO occurring in AVS. […] The major objective of this review is to present the case that pathogenesis of AS is an active process that involves a combination of inflammatory activation, increased oxidative stress, fibrosis and calcification, which should be amenable to therapeutic intervention.

• #19 Aortic stenosis: a review on acquired pathogenesis and ominous combination with diabetes mellitus | The Egyptian Heart Journal | Full Text

  https://tehj.springeropen.com/articles/10.1186/s43044-023-00345-6

  The infiltration of monocytes, mast cells, T cells, and lipoproteins (such low-density lipoprotein (LDL), lipoprotein(a)), which promotes inflammation and fat build-up, is made easier by the loss of endothelial integrity. […] Valvular calcification, which is facilitated by dystrophic calcification and biomineralisation, is another significant step of the propagation phase.

• #20 Investigating the mechanism of aortic valve stenosis: the role of magnesium salts | Journal of Cardiothoracic Surgery | Full Text

  https://cardiothoracicsurgery.biomedcentral.com/articles/10.1186/1749-8090-8-S1-O18

  The calcification of aortic valves is a common disease and valve replacement is the only established treatment. Herewith, we use infrared (FT-IR) spectroscopy to investigate and characterize the mineral deposits in order to understand the mechanism of aortic valve calcification and stenosis. […] The changes of FT-IR spectra at 1743 cm-1 resulted from hyperoxidation of lipids due to oxidative stress. The characteristic bands at the spectral regions 1200-900 cm-1 and 700-400 cm-1 showed the formation of low crystallinity biological hydroxyapatite (Ca10(PO4)6(OH)2) and calcium monophosphate (CaHPO4) salts. […] The findings confirmed the hypothesis that hydroxyapatite is formed predominantly due to ATP cycle, where the release of phosphate anions take place in ischemic pathways. […] The characteristic FT-IR absorption bands of calcified aortic valves showed hyperoxidation of membranes (a pro-inflammation stage), while the mineral deposits were consistent of low crystallinity biological hydroxyapatite, Ca2HPO4 and calcium phosphates. SEM-EDAX data showed substitution of calcium cations from magnesium cations leading to amorphous salts, preventing thus the aortic valve stenosis. Treatment of these patients with magnesium salts maybe could reduce the progress of aortic valve stenosis after valve replacement.

• #21 Pathogenesis of aortic stenosis: not just a matter of wear and tear

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3253493/

  Aortic valve stenosis (AS) is the commonest form of valvular heart disease in the Western world. […] Although risk factors and downstream mediators appear similar for AS and atherosclerosis (older age, male sex, hypertension, smoking, hypercholesterolemia, and diabetes, as many as 50% of patients with AS do not have clinically significant atherosclerosis. […] On the basis both of recent experimental evidence and clinical trials, it appears that atherogenesis is not pivotal to the pathogenesis of AS. […] On the other hand, there is increasing evidence of active involvement of aortic valve fibroblasts with resultant increased production of reactive oxygen species, active pro-inflammatory and pro-fibrotic processes culminating in calcification. […] The renin-angiotensin system has also emerged as a major player in the pathogenesis of AS.

• #22 Aortic Stenosis – Cardiovascular Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/cardiovascular-disorders/valvular-disorders/aortic-stenosis

  Aortic stenosis (AS) is narrowing of the aortic valve, obstructing blood flow from the left ventricle to the ascending aorta during systole. […] The cause of aortic sclerosis and stenosis is not yet known but is mediated by an inflammatory process that is similar to but distinct from atherosclerosis. Genetic, anatomic, fluid dynamic, and environmental risk factors include hypertension, smoking, high cholesterol, and presence of a bicuspid valve. Lipid deposition and inflammation lead to thickening of aortic valve structures by fibrosis and calcification initially without causing significant obstruction. Over years, aortic sclerosis progresses to stenosis in as many as 15% of patients. […] Lipoprotein (a) is implicated in the pathogenesis of both aortic stenosis and atherosclerosis. Elevated lipoprotein (a) levels also predict faster hemodynamic progression of AS.

• #23 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  There may exist a causal association between LDL-C-related genetic variants and aortic valve disease. In a community-based study consisting of 6942 subjects with data on aortic valve calcium and more than 28,000 subjects with aortic stenosis (follow-up, 16 y), Smith et al found that genetic predisposition toward elevations in low-density lipoprotein cholesterol (LDL-C) (as indicated by genetic risk scores [GRSs]) but not elevated high-density lipoprotein cholesterol (HDL-C) or triglycerides GRSs were associated with the presence of aortic valve calcium and the incidence of aortic stenosis.

• #24 Genome-wide analysis yields new loci associating with aortic valve stenosis | Nature Communications

  https://www.nature.com/articles/s41467-018-03252-6

  Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. […] The pathogenesis of the disease remains poorly understood. However, several of the associated clinical risk factors of calcified aortic valve are shared by atherosclerotic disease, and immunohistochemical studies show that calcified aortic valve lesions have many characteristic features of atherosclerosis, including initial endothelial damage, oxidized lipid deposition, chronic inflammation, and calcification. […] The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. […] Given that several atherosclerosis risk factors have been associated with AS, we tested the novel AS variants for association with the traditional cardiovascular risk factors and observed a nominally significant association between rs1830321 and systolic and diastolic blood pressure in Iceland.

• #25 Novel Circulating Biomarkers in Aortic Valve Stenosis

  https://www.mdpi.com/1422-0067/26/5/1902

  The underlying pathophysiology of aortic stenosis and factors affecting its clinical progression remain poorly understood. […] Among the biomarkers studied, lipoprotein(a) [Lp(a)] has emerged as the most promising for risk stratification. Elevated Lp(a) levels are often associated with more rapid aortic stenosis progression. This detrimental effect is attributed to its role in promoting valve calcification. […] While once viewed as a passive, age-related process, aortic stenosis is now recognised as an active disease. Its progression can be divided into two phases: initiation and propagation. The initiation phase involves endothelial injury and the subsequent infiltration of Lp(a) and low-density lipoproteins (LDLs) into the valve. […] The subsequent propagation phase is mainly characterised by fibrosis and calcification. Inflammation-activated vascular interstitial cells contribute to fibrosis by secreting matrix metalloproteinases (MMPs) and adopting a myofibroblastic phenotype.

• #26 Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA

  https://www.mdpi.com/1422-0067/24/19/14939

  Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA […] Aortic valve stenosis (AVS) is the most frequent cardiac valve disease in the general population (0.4%), affecting 2% of subjects aged 65 and 12% of patients aged greater than 75. The degenerative/calcific (or senile) cause is the most common type of aortic stenosis in the elderly population; its incidence increases with age and is due to the establishment of fibrocalcific processes. The prognosis is unfavorable from the onset of typical symptoms: angina, syncope, and heart failure. In the absence of specific treatment, the onset of symptoms is associated with a survival rate of 50% at a 2-year follow-up. […] The history of aortic stenosis has radically evolved in recent decades. Initially, the pathological process was thought to be related to wear and tear. However, it has been shown that the mechanisms responsible for aortic stenosis are processes that are more similar to atherosclerosis. The pathogenesis is linked to an activity involving genetic mechanisms, lipoproteins, inflammation, and mineralization of the valve leaflets. The process results in valve stenosis with obstruction of flow from the left ventricle to the systemic circulation.

• #27 Novel Circulating Biomarkers in Aortic Valve Stenosis

  https://www.mdpi.com/1422-0067/26/5/1902

  Elevated Lp(a) levels may contribute to aortic valve calcification by activating the autotaxin-lysophosphatidic acid signalling pathway in the valvular interstitial cells. […] While elevated Lp(a) levels are often associated with faster disease progression in aortic stenosis, studies have demonstrated a strong association between elevated Lp(a) and the development of subclinical asymptomatic aortic sclerosis, characterised by valve thickening without significant obstruction to blood flow. […] Recent research suggests that targeting TGF-β1 may be a promising therapeutic strategy for aortic stenosis, supported by the detection of increased TGF-β1 expression in human aortic stenosis biopsies. […] Matrix metalloproteinases (MMPs) are key proteases involved in extracellular matrix degradation, one of the critical processes in aortic stenosis progression.

• #28 Aortic stenosis: a review on acquired pathogenesis and ominous combination with diabetes mellitus | The Egyptian Heart Journal | Full Text

  https://tehj.springeropen.com/articles/10.1186/s43044-023-00345-6

  Aortic stenosis (AS) is a progressive disease, with no pharmacological treatment. […] The interplay between AS and DM’s mechanism is not entirely known yet. […] The increased accumulation of advanced glycation end products (AGEs) was linked to increased valvular oxidative stress, inflammation, expression of coagulation factors, and signs of calcification, according to an analysis of aortic stenotic valves. […] It has been suggested that hyperglycemia, along with other metabolic variables, may start or at least exacerbate valvular calcification through some kind of complicated process involving interactions between vascular and inflammatory cells. […] An increase in valvular protein glycation brought on by an aggregation of enhanced glycation end products (AGEs) is indicated as a factor in the accelerated course of AS.

• #29 Aortic stenosis: a review on acquired pathogenesis and ominous combination with diabetes mellitus | The Egyptian Heart Journal | Full Text

  https://tehj.springeropen.com/articles/10.1186/s43044-023-00345-6

  The build-up of AGEs in aortic valves led to the osteoblastic development of VICs, as demonstrated by the rabbit mouse models of AS. […] A 6.6- and 12-fold rise in valvular plasma AGEs was linked with AS severity, defined by the decreased aortic valve area, in AS patients with concurrent DM. […] This impact of AGEs on AS development was recently demonstrated in these individuals. […] The aortic valve side experiences a focal stiffening of the valves in the early stages of the illness, which starts just at subendothelial level and thereafter progresses to the outermost or fibrous layer. […] The aortic valve becomes substantially stiffer and has a significantly smaller valvular area as a result of the regions of thickening converging into huge calcified masses over time. […] The process starts in these regions of higher mechanical stress, while bending force, pressure, and shear forces will cause damage to the structural integrity of the leaflet tissue and induce calcification.

• #30 Novel Circulating Biomarkers in Aortic Valve Stenosis

  https://www.mdpi.com/1422-0067/26/5/1902

  Elevated Lp(a) levels may contribute to aortic valve calcification by activating the autotaxin-lysophosphatidic acid signalling pathway in the valvular interstitial cells. […] While elevated Lp(a) levels are often associated with faster disease progression in aortic stenosis, studies have demonstrated a strong association between elevated Lp(a) and the development of subclinical asymptomatic aortic sclerosis, characterised by valve thickening without significant obstruction to blood flow. […] Recent research suggests that targeting TGF-β1 may be a promising therapeutic strategy for aortic stenosis, supported by the detection of increased TGF-β1 expression in human aortic stenosis biopsies. […] Matrix metalloproteinases (MMPs) are key proteases involved in extracellular matrix degradation, one of the critical processes in aortic stenosis progression.

• #31 Novel Circulating Biomarkers in Aortic Valve Stenosis

  https://www.mdpi.com/1422-0067/26/5/1902

  Recent studies have highlighted the role of monocytes and macrophages in the progression of aortic stenosis. Monocytes infiltrate the aortic valve, subsequently becoming macrophages that take up oxidised lipids, contribute to inflammation and promote calcification of the aortic valve. […] The emerging field of microbiota-derived metabolites has garnered significant interest in recent years, with implications for various seemingly unrelated health conditions, including aortic stenosis. In particular, trimethylamine N-oxide (TMAO) has been implicated in the pathogenesis of aortic stenosis.

• #32 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  When the aortic valve becomes stenotic, resistance to systolic ejection occurs and a systolic pressure gradient develops between the left ventricle and the aorta. This outflow obstruction leads to an increase in left ventricular (LV) systolic pressure. As a compensatory mechanism to normalize LV wall stress, LV wall thickness increases by parallel replication of sarcomeres, producing concentric hypertrophy. At this stage, the chamber is not dilated and ventricular function is preserved, although diastolic compliance is reduced. […] Eventually, however, LV end-diastolic pressure (LVEDP) rises, which causes a corresponding increase in pulmonary capillary arterial pressures and a decrease in cardiac output due to diastolic dysfunction. The contractility of the myocardium may also diminish, which leads to a decrease in cardiac output due to systolic dysfunction. Ultimately, heart failure develops.

• #33 CV Physiology | Valvular Stenosis

  https://cvphysiology.com/heart-disease/hd004

  Aortic valve stenosis is characterized by the left ventricular pressure being much greater than aortic pressure during left ventricular (LV) ejection. […] The elevated pressure gradient across the stenotic valve results from both increased resistance (related to narrowing of the valve opening) and turbulence distal to the valve. Increased flow across the valve enhances the magnitude of the pressure gradient (e.g., during exercise). […] Because the ventricle is required to generate greater pressures, this leads to ventricular hypertrophy (thickening of the muscular walls) and diastolic dysfunction (impaired filling). […] Aortic valve stenosis is associated with a mid-systolic murmur because of turbulence that occurs as blood flows across the stenotic valve. […] Aortic stenosis alters left ventricular pressure (LVP), aortic pressure (AP) and left atrial pressure (LAP) during the cardiac cycle. […] Such measurements of LVP and AP by cardiac catheterization provide a quantitative, hemodynamic assessment of the severity of stenosis.

• #34 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  When the aortic valve becomes stenotic, resistance to systolic ejection occurs and a systolic pressure gradient develops between the left ventricle and the aorta. This outflow obstruction leads to an increase in left ventricular (LV) systolic pressure. As a compensatory mechanism to normalize LV wall stress, LV wall thickness increases by parallel replication of sarcomeres, producing concentric hypertrophy. At this stage, the chamber is not dilated and ventricular function is preserved, although diastolic compliance is reduced. […] Eventually, however, LV end-diastolic pressure (LVEDP) rises, which causes a corresponding increase in pulmonary capillary arterial pressures and a decrease in cardiac output due to diastolic dysfunction. The contractility of the myocardium may also diminish, which leads to a decrease in cardiac output due to systolic dysfunction. Ultimately, heart failure develops.

• #35 Aortic stenosis – Wikipedia

  https://en.wikipedia.org/wiki/Aortic_stenosis

  As a consequence of this stenosis, the left ventricle must generate a higher pressure with each contraction to effectively move blood forward into the aorta. Initially, the LV generates this increased pressure by thickening its muscular walls (myocardial hypertrophy). The type of hypertrophy most commonly seen in AS is known as concentric hypertrophy, in which the walls of the LV are (approximately) equally thickened. […] In the later stages, the left ventricle dilates, the wall thins, and the systolic function deteriorates (resulting in impaired ability to pump blood forward).

• #36 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  When the aortic valve becomes stenotic, resistance to systolic ejection occurs and a systolic pressure gradient develops between the left ventricle and the aorta. This outflow obstruction leads to an increase in left ventricular (LV) systolic pressure. As a compensatory mechanism to normalize LV wall stress, LV wall thickness increases by parallel replication of sarcomeres, producing concentric hypertrophy. At this stage, the chamber is not dilated and ventricular function is preserved, although diastolic compliance is reduced. […] Eventually, however, LV end-diastolic pressure (LVEDP) rises, which causes a corresponding increase in pulmonary capillary arterial pressures and a decrease in cardiac output due to diastolic dysfunction. The contractility of the myocardium may also diminish, which leads to a decrease in cardiac output due to systolic dysfunction. Ultimately, heart failure develops.

• #37 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  Increased LV mass, increased LV systolic pressure, and prolongation of the systolic ejection phase all elevate the myocardial oxygen requirement, especially in the subendocardial region. Although coronary blood flow may be normal when corrected for LV mass, coronary flow reserve is often reduced. […] Myocardial perfusion is thus compromised by the relative decline in myocardial capillary density and by a reduced diastolic transmyocardial (coronary) perfusion gradient due to elevated LV diastolic pressure. Therefore, the subendocardium is susceptible to underperfusion, which results in myocardial ischemia. […] Angina results from a concomitant increased oxygen requirement by the hypertrophic myocardium and diminished oxygen delivery secondary to diminished coronary flow reserve, decreased diastolic perfusion pressure, and relative subendocardial myocardial ischemia.

• #38 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  Increased LV mass, increased LV systolic pressure, and prolongation of the systolic ejection phase all elevate the myocardial oxygen requirement, especially in the subendocardial region. Although coronary blood flow may be normal when corrected for LV mass, coronary flow reserve is often reduced. […] Myocardial perfusion is thus compromised by the relative decline in myocardial capillary density and by a reduced diastolic transmyocardial (coronary) perfusion gradient due to elevated LV diastolic pressure. Therefore, the subendocardium is susceptible to underperfusion, which results in myocardial ischemia. […] Angina results from a concomitant increased oxygen requirement by the hypertrophic myocardium and diminished oxygen delivery secondary to diminished coronary flow reserve, decreased diastolic perfusion pressure, and relative subendocardial myocardial ischemia.

• #39 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  Increased LV mass, increased LV systolic pressure, and prolongation of the systolic ejection phase all elevate the myocardial oxygen requirement, especially in the subendocardial region. Although coronary blood flow may be normal when corrected for LV mass, coronary flow reserve is often reduced. […] Myocardial perfusion is thus compromised by the relative decline in myocardial capillary density and by a reduced diastolic transmyocardial (coronary) perfusion gradient due to elevated LV diastolic pressure. Therefore, the subendocardium is susceptible to underperfusion, which results in myocardial ischemia. […] Angina results from a concomitant increased oxygen requirement by the hypertrophic myocardium and diminished oxygen delivery secondary to diminished coronary flow reserve, decreased diastolic perfusion pressure, and relative subendocardial myocardial ischemia.

• #40 Aortic Stenosis: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2008/0915/p717.html

  As aortic stenosis worsens, with the aortic valve area decreasing to 1 cm2 or less (about the size of the head of a golf tee), changes in LV function may no longer be adequate to overcome the outflow obstruction and maintain systolic function, even when complemented by an increase in preload. […] Progressive LV hypertrophy from aortic stenosis also leads to increased myocardial oxygen needs; concurrently, myocardial hypertrophy may compress the intramural coronary arteries as they carry blood toward the endocardium. […] These changes along with reduced diastolic filling of the coronary arteries may result in classic angina, even in the absence of coronary artery disease (CAD). […] In addition, as aortic stenosis becomes severe, cardiac output no longer increases with exercise.

• #41 Aortic Stenosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150638-overview

  In most patients with aortic stenosis, LV systolic function is preserved and cardiac output is maintained for many years despite an elevated LV systolic pressure. Although cardiac output is normal at rest, it often fails to increase appropriately during exercise, which may result in exercise-induced symptoms. […] Diastolic dysfunction may occur as a consequence of impaired LV relaxation and/or decreased LV compliance, as a result of increased afterload, LV hypertrophy, or myocardial ischemia. LV hypertrophy often regresses following relief of valvular obstruction. However, some individuals develop extensive myocardial fibrosis, which may not resolve despite regression of hypertrophy. […] In patients with severe aortic stenosis, atrial contraction plays a particularly important role in diastolic filling of the LV. Thus, development of atrial fibrillation in aortic stenosis often leads to heart failure due to an inability to maintain cardiac output.

• #42 Aortic stenosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Aortic_stenosis_pathophysiology

  However, left ventricle hypertrophy ends up being a maladaptive mechanism and a marker of a bad prognosis. […] Myocardial scarring or fibrosis may develop with prolonged aortic stenosis, probably due to chronic subendocardial ischemia or increased wall stress. […] The stiff non-compliant left ventricle can become increasingly dependent on the left atrium for filling, which predisposes to atrial fibrillation.

• #43 Aortic stenosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Aortic_stenosis_pathophysiology

  However, left ventricle hypertrophy ends up being a maladaptive mechanism and a marker of a bad prognosis. […] Myocardial scarring or fibrosis may develop with prolonged aortic stenosis, probably due to chronic subendocardial ischemia or increased wall stress. […] The stiff non-compliant left ventricle can become increasingly dependent on the left atrium for filling, which predisposes to atrial fibrillation.

• #44 Sudden Cardiac Arrest in Patient with Aortic Stenosis and Preexcitation

  https://clinmedjournals.org/articles/ijcc/international-journal-of-clinical-cardiology-ijcc-9-259.php?jid=ijcc

  Aortic stenosis as well as preexcitation can lead to sudden cardiac arrest. […] Echocardiogram showed thickened calcified aortic valve and severe AS with calculated aortic valve area of 0.66 cm², mean aortic valve gradient of 6.9 mmHg and peak velocity across aortic valve of 2.09 m/s. […] The underlying mechanism of sudden cardiac death and aortic stenosis are following: 1) Abnormal Bezold-Jarisch reflex: Aortic stenosis leads to activation of left ventricular baroreceptors that cause hypotension and bradycardia leading to sudden cardiac death. In addition, these factors also contribute to decrease coronary blood supply resulting in myocardial ischemia and further leading to malignant tachycardia and sudden cardiac death. 2) Left ventricular hypertrophy: This leads to increased myocardial oxygen consumption and reduced coronary blood flow reserve. 3) Atrioventricular conduction disturbances: This results from contiguity between valvular-perivalvular calcification in his-Purkinje system.

• #45 Sudden Cardiac Arrest in Patient with Aortic Stenosis and Preexcitation

  https://clinmedjournals.org/articles/ijcc/international-journal-of-clinical-cardiology-ijcc-9-259.php?jid=ijcc

  Mechanical explanation of ventricular arrhythmias and aortic stenosis: Aortic stenosis leads to systolic pressure overload which causes myocardial hypertrophy in leads to structural remodeling with increased collagen, abnormal electrophysiological properties, decreased myocardial perfusion due to reduced coronary vasodilator reserve further leading to myocardial ischemia, myocardial death and scar formation. […] Electrophysiological mechanism of ventricular arrhythmia and aortic stenosis: This is resultant from reentry, stress-induced arrhythmia as well as triggered activity. […] Our patient had low output low gradient aortic stenosis which is defined as aortic stenosis with calculated valve area of less than 1 cm² and presence of left ventricular dysfunction with left ventricular ejection fraction of less than 40% along with low cardiac output and low transaortic mean gradient of less than 30 mmHg. Modified dobutamine stress test can help differentiate true aortic stenosis from severe aortic stenosis and is also a predictor of worse outcome if there is no change in cardiac output.

• #46 Aortic Stenosis – Cardiovascular Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/cardiovascular-disorders/valvular-disorders/aortic-stenosis

  The increased pressure load imposed by aortic stenosis results in compensatory hypertrophy of the left ventricle (LV) without cavity enlargement (concentric hypertrophy). With time, the ventricle can no longer compensate, causing secondary LV cavity enlargement, reduced ejection fraction (EF), decreased cardiac output, and a misleadingly low gradient across the aortic valve (low-gradient severe AS). […] Elevated shear stress across the stenosed aortic valve degrades von Willebrand factor multimers. The resulting coagulopathy may cause gastrointestinal bleeding in patients with angiodysplasia (Heyde syndrome).

• #47 Aortic valve sclerosis: Pathogenesis, clinical manifestations, diagnosis and management – UpToDate

  https://www.uptodate.com/contents/aortic-valve-sclerosis-pathogenesis-clinical-manifestations-diagnosis-and-management

  Aortic valve sclerosis is important clinically because it progresses to aortic stenosis in a minority of patients and is associated with increased cardiovascular risk, although this association does not appear to be causal. […] This topic will discuss the pathogenesis of aortic sclerosis and calcific aortic stenosis and the diagnosis, prevalence, clinical significance, and management of aortic sclerosis. […] Aortic sclerosis is defined as irregular thickening and/or calcification of the valve leaflets without stenosis (ie, antegrade transvalvular velocity is ≤2 m/s). […] The prevalence of aortic valve sclerosis detected by echocardiography increases with age from <10 percent at mean age less than 60 years to 35 percent between 75 and 84 years of age and approximately 50 percent of those over age 80.

• #48 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  The propagation phase of CAS is characterised by repeated fibrosis and calcification. Inflammation activated VICs induce fibrosis by the secretion of matrix metalloproteinases through a myofibroblastic phenotype. […] This scarred tissue acts as a nidus for calcification in which inflammation-induced apoptosis of VICs leads to diffuse microcalcification through the release of apoptotic bodies. […] As the disease progresses, stiffening of the valve prompts further apoptosis, resulting in the calcific mechanisms superseding the immunological pathway in propagating CAS. […] The macroscopic manifestations of CAS, as a result of cellular pathological processes, affect the aortic valve and surrounding myocardium. Initially, valve disease is difficult to detect. […] Within 7 years, 10% of these patients would progress to CAS, distinguished by restricted valve motion and haemodynamic obstruction.

• #49 Aortic Stenosis: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2008/0915/p717.html

  Aortic stenosis is the most important cardiac valve disease in developed countries, affecting 3 percent of persons older than 65 years. […] The pathology of aortic stenosis includes processes similar to those in atherosclerosis, including lipid accumulation, inflammation, and calcification. […] The development of significant aortic stenosis tends to occur earlier in those with congenital bicuspid aortic valves. […] As the aortic valve area becomes less than one half its normal size of 3 to 4 cm2 (about the size of a nickel), a measurable pressure gradient between the left ventricle and ascending aorta may be detected on echocardiography or by direct measurement at cardiac catheterization. […] One consequence is LV hypertrophy with subsequent diastolic dysfunction and increased resistance to LV filling.

• #50 Aortic Stenosis: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2008/0915/p717.html

  As aortic stenosis worsens, with the aortic valve area decreasing to 1 cm2 or less (about the size of the head of a golf tee), changes in LV function may no longer be adequate to overcome the outflow obstruction and maintain systolic function, even when complemented by an increase in preload. […] Progressive LV hypertrophy from aortic stenosis also leads to increased myocardial oxygen needs; concurrently, myocardial hypertrophy may compress the intramural coronary arteries as they carry blood toward the endocardium. […] These changes along with reduced diastolic filling of the coronary arteries may result in classic angina, even in the absence of coronary artery disease (CAD). […] In addition, as aortic stenosis becomes severe, cardiac output no longer increases with exercise.

• #51 Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA

  https://www.mdpi.com/1422-0067/24/19/14939

  Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA […] Aortic valve stenosis (AVS) is the most frequent cardiac valve disease in the general population (0.4%), affecting 2% of subjects aged 65 and 12% of patients aged greater than 75. The degenerative/calcific (or senile) cause is the most common type of aortic stenosis in the elderly population; its incidence increases with age and is due to the establishment of fibrocalcific processes. The prognosis is unfavorable from the onset of typical symptoms: angina, syncope, and heart failure. In the absence of specific treatment, the onset of symptoms is associated with a survival rate of 50% at a 2-year follow-up. […] The history of aortic stenosis has radically evolved in recent decades. Initially, the pathological process was thought to be related to wear and tear. However, it has been shown that the mechanisms responsible for aortic stenosis are processes that are more similar to atherosclerosis. The pathogenesis is linked to an activity involving genetic mechanisms, lipoproteins, inflammation, and mineralization of the valve leaflets. The process results in valve stenosis with obstruction of flow from the left ventricle to the systemic circulation.

• #52 Aortic stenosis | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/cardiovascular-intensive-care/Chapter-36/aortic-stenosis

  The college is particularly fond of aortic stenosis, as is demonstrated by their constant asking of questions on this topic. […] An even more interesting matter is what to do when these AS patients have their valve replaced. The consequences of exposing the systemic circulation to a massively overpowered LV are worth discussing. […] In summary, for severe aortic stenosis: […] A balloon pump might be of some use if the patient is in cardiogenic shock. […] Mild stenosis is compensated for by LV hypertrophy, as the LV is expected to generate an increasing pressure to drive blood across the narrowing valve. […] The ventricle loses its contractility and coronary perfusion pressure decreases due to an elevated LVEDP. […] Critical stenosis represents an aortic valve index below 0.5cm²/m². At this stage, pulmonary venous hypertension develops. […] If you manage to survive all this, right ventricular failure will eventually develop.

• #53 Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis | Open Heart

  https://openheart.bmj.com/content/10/1/e002244

  Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the conditions mechanistic underpinning has shifted the paradigm to an active disease process. […] The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options. […] The precise pathological mechanism behind the stenosis of the aortic valve remains unresolved. Nonetheless, advancements in technology and research have changed our insight. A once considered passive, degenerative process due to ageing is now understood to be active, similar in its molecular underpinning to atherosclerosis and its associated inflammatory response.

• #54 Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA

  https://www.mdpi.com/1422-0067/24/19/14939

  Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA […] Aortic valve stenosis (AVS) is the most frequent cardiac valve disease in the general population (0.4%), affecting 2% of subjects aged 65 and 12% of patients aged greater than 75. The degenerative/calcific (or senile) cause is the most common type of aortic stenosis in the elderly population; its incidence increases with age and is due to the establishment of fibrocalcific processes. The prognosis is unfavorable from the onset of typical symptoms: angina, syncope, and heart failure. In the absence of specific treatment, the onset of symptoms is associated with a survival rate of 50% at a 2-year follow-up. […] The history of aortic stenosis has radically evolved in recent decades. Initially, the pathological process was thought to be related to wear and tear. However, it has been shown that the mechanisms responsible for aortic stenosis are processes that are more similar to atherosclerosis. The pathogenesis is linked to an activity involving genetic mechanisms, lipoproteins, inflammation, and mineralization of the valve leaflets. The process results in valve stenosis with obstruction of flow from the left ventricle to the systemic circulation.

• #55 Pathogenesis and pathophysiology of aortic valve stenosis in adults – Polish Archives of Internal Medicine

  https://www.mp.pl/paim/issue/article/1103

  Aortic stenosis (AS) is the most common form of valvular heart disease. AS of degenerative etiology is predominant. It is a persistent disease associated with the activation of 3 processes: lipid accumulation, inflammation, and calcification. Recent studies suggest that valve calcification is an actively regulated process that involves extracellular matrix remodeling, angiogenesis, and inflammation leading to bone formation. Many mechanisms and risk factors involved in the pathogenesis of AS are similar to those observed in atherosclerosis. […] The knowledge of these processes may play a significant role in adequate prevention and therapy of patients with AS, especially at an early stage.

• #56 Aortic stenosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Aortic_stenosis_pathophysiology

  Aortic stenosis is the progressive narrowing of the aortic valve. […] Calcific aortic stenosis, in particular, is an active atherosclerotic pathology where inflammation, fibrosis, and calcification are involved in the progressive narrowing of the effective aortic valve area in the absence of any commissural fusion. […] Aortic stenosis causes an impedance to the antegrade blood flow not only at the level of the aortic valve itself but also at the subvalvular (below the aortic valve) or supravalvular (above the aortic valve) levels. As a result, chronic pressure overload develops in the left ventricle. […] Slow compensatory mechanisms occur in the heart to adapt to the pressure changes caused by aortic stenosis. The most prominent adaptive mechanism is ventricular hypertrophy which leads early on to diastolic dysfunction and later on to systolic dysfunction.

• #57 Comorbidities and Aortic Valve Stenosis: Molecular mechanism, risk factors and novel therapeutic options | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/15053/comorbidities-and-aortic-valve-stenosis-molecular-mechanism-risk-factors-and-novel-therapeutic-options/articles

  Aortic valve stenosis (AS) is the most prevalent valvular heart disease of the elderly population in the developed world, and the disease burden is estimated to increase from 2.5 million in 2000 to 4.5 million in 2030. […] Given the increasing number of elderly patients with many comorbidities, there is an urgent need for a better understanding of how these disease states influence the mechanism of AS initiation and progression and the underlying pathologies like fibrosis and calcification. […] The aim of this Research Topic is to gather contributions from interdisciplinary scientists working in basic, translational and clinical research exploring the interplay between aortic stenosis pathogenesis and co-morbid states, with mutual interests in elucidating the pathological molecular mechanisms, risk factors and therapeutic options to discover new mechanistic and clinical understanding of AS and comorbidities.

• #58 Current Strategies in the Management of Aortic Stenosis | USC Journal

  https://www.uscjournal.com/articles/final-word-current-strategies-lifetime-management-patients-aortic-valve-stenosis

  Another plausible mechanism is mediated by the renin-angiotensin-aldosterone system through the promotion of monocytes infiltration, inflammatory cytokines production, and differentiation of aortic valve interstitial cells into osteoblast-like cells. […] Over time, all these processes lead to valve degeneration and calcification. Valve leaflet thickening, along with the resultant reduction in the aortic valve area, increase left ventricular afterload, which in turn leads to ventricular remodeling, fibrosis, and diastolic dysfunction. […] As valvular degeneration progresses in severity, systolic dysfunction ensues, and the risk of lethal arrhythmias rises. Therefore, different mechanisms are involved in the pathogenesis and progression of AS, and thus may be targeted by medical therapy. […] Ongoing clinical trials are currently testing the effects of medications that target calcium metabolic pathways on the progression of calcific aortic stenosis.

• #59 Current Strategies in the Management of Aortic Stenosis | USC Journal

  https://www.uscjournal.com/articles/final-word-current-strategies-lifetime-management-patients-aortic-valve-stenosis

  Another plausible mechanism is mediated by the renin-angiotensin-aldosterone system through the promotion of monocytes infiltration, inflammatory cytokines production, and differentiation of aortic valve interstitial cells into osteoblast-like cells. […] Over time, all these processes lead to valve degeneration and calcification. Valve leaflet thickening, along with the resultant reduction in the aortic valve area, increase left ventricular afterload, which in turn leads to ventricular remodeling, fibrosis, and diastolic dysfunction. […] As valvular degeneration progresses in severity, systolic dysfunction ensues, and the risk of lethal arrhythmias rises. Therefore, different mechanisms are involved in the pathogenesis and progression of AS, and thus may be targeted by medical therapy. […] Ongoing clinical trials are currently testing the effects of medications that target calcium metabolic pathways on the progression of calcific aortic stenosis.

• #60 Investigating the mechanism of aortic valve stenosis: the role of magnesium salts | Journal of Cardiothoracic Surgery | Full Text

  https://cardiothoracicsurgery.biomedcentral.com/articles/10.1186/1749-8090-8-S1-O18

  The calcification of aortic valves is a common disease and valve replacement is the only established treatment. Herewith, we use infrared (FT-IR) spectroscopy to investigate and characterize the mineral deposits in order to understand the mechanism of aortic valve calcification and stenosis. […] The changes of FT-IR spectra at 1743 cm-1 resulted from hyperoxidation of lipids due to oxidative stress. The characteristic bands at the spectral regions 1200-900 cm-1 and 700-400 cm-1 showed the formation of low crystallinity biological hydroxyapatite (Ca10(PO4)6(OH)2) and calcium monophosphate (CaHPO4) salts. […] The findings confirmed the hypothesis that hydroxyapatite is formed predominantly due to ATP cycle, where the release of phosphate anions take place in ischemic pathways. […] The characteristic FT-IR absorption bands of calcified aortic valves showed hyperoxidation of membranes (a pro-inflammation stage), while the mineral deposits were consistent of low crystallinity biological hydroxyapatite, Ca2HPO4 and calcium phosphates. SEM-EDAX data showed substitution of calcium cations from magnesium cations leading to amorphous salts, preventing thus the aortic valve stenosis. Treatment of these patients with magnesium salts maybe could reduce the progress of aortic valve stenosis after valve replacement.

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