The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Philippe Sucosky - One of the best experts on this subject based on the ideXlab platform.
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defining the role of fluid shear stress in the expression of early signaling markers for calcific Aortic Valve Disease
PLOS ONE, 2013Co-Authors: Nalini M Rajamannan, Philippe SucoskyAbstract:Calcific Aortic Valve Disease (CAVD) is an active process presumably triggered by interplays between cardiovascular risk factors, molecular signaling networks and hemodynamic cues. While earlier studies demonstrated that alterations in fluid shear stress (FSS) on the fibrosa could trigger inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. This knowledge could be critical to the elucidation of key CAVD risk factors such as congenital Valve defects, aging and hypertension, which are known to generate FSS disturbances. The objective of this study was to characterize ex vivo the contribution of isolated and combined abnormalities in FSS magnitude and frequency to early valvular pathogenesis. The ventricularis and fibrosa of porcine Aortic Valve leaflets were exposed simultaneously to different combinations of sub-physiologic/physiologic/supra-physiologic levels of FSS magnitude and frequency for 24, 48 and 72 hours in a double cone-and-plate device. Endothelial activation and paracrine signaling were investigated by measuring cell-adhesion molecule (ICAM-1, VCAM-1) and cytokine (BMP-4, TGF-β1) expressions, respectively. Extracellular matrix (ECM) degradation was characterized by measuring the expression and activity of the proteases MMP-2, MMP-9, cathepsin L and cathepsin S. The effect of the FSS treatment yielding the most significant pathological response was examined over a 72-hour period to characterize the time-dependence of FSS mechano-transduction. While cytokine expression was stimulated under elevated FSS magnitude at normal frequency, ECM degradation was stimulated under both elevated FSS magnitude at normal frequency and physiologic FSS magnitude at abnormal frequency. In contrast, combined FSS magnitude and frequency abnormalities essentially maintained valvular homeostasis. The pathological response under supra-physiologic FSS magnitude peaked at 48 hours but was then maintained until the 72-hour time point. This study confirms the sensitivity of Valve leaflets to both FSS magnitude and frequency and suggests the ability of supra-physiologic FSS levels or abnormal FSS frequencies to initiate CAVD mechanisms.
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ex vivo evidence for the contribution of hemodynamic shear stress abnormalities to the early pathogenesis of calcific bicuspid Aortic Valve Disease
PLOS ONE, 2012Co-Authors: Ling Sun, Santanu Chandra, Philippe SucoskyAbstract:The bicuspid Aortic Valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific Aortic Valve Disease (CAVD). The most prevalent type-I morphology, which results from left-/right-coronary cusp fusion, generates different hemodynamics than a tricuspid Aortic Valve (TAV). While valvular calcification has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors. In particular, the wall shear stress (WSS) produced by blood flow on the leaflets regulates homeostasis in the TAV. In contrast, WSS alterations cause Valve dysfunction and Disease. While such observations support the existence of synergies between valvular hemodynamics and biology, the role played by BAV WSS in valvular calcification remains unknown. The objective of this study was to isolate the acute effects of native BAV WSS abnormalities on CAVD pathogenesis. Porcine Aortic Valve leaflets were subjected ex vivo to the native WSS experienced by TAV and type-I BAV leaflets for 48 hours. Immunostaining, immunoblotting and zymography were performed to characterize endothelial activation, pro-inflammatory paracrine signaling, extracellular matrix remodeling and markers involved in valvular interstitial cell activation and osteogenesis. While TAV and non-coronary BAV leaflet WSS essentially maintained valvular homeostasis, fused BAV leaflet WSS promoted fibrosa endothelial activation, paracrine signaling (2.4-fold and 3.7-fold increase in BMP-4 and TGF-β1, respectively, relative to fresh controls), catabolic enzyme secretion (6.3-fold, 16.8-fold, 11.7-fold, 16.7-fold and 5.5-fold increase in MMP-2, MMP-9, cathepsin L, cathepsin S and TIMP-2, respectively) and activity (1.7-fold and 2.4-fold increase in MMP-2 and MMP-9 activity, respectively), and bone matrix synthesis (5-fold increase in osteocalcin). In contrast, BAV WSS did not significantly affect α-SMA and Runx2 expressions and TIMP/MMP ratio. This study demonstrates the key role played by BAV hemodynamic abnormalities in CAVD pathogenesis and suggests the dependence of BAV vulnerability to calcification on the local degree of WSS abnormality.
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computational assessment of bicuspid Aortic Valve wall shear stress implications for calcific Aortic Valve Disease
Biomechanics and Modeling in Mechanobiology, 2012Co-Authors: Santanu Chandra, Nalini M Rajamannan, Philippe SucoskyAbstract:The bicuspid Aortic Valve (BAV) is associated with a high prevalence of calcific Aortic Valve Disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid Aortic Valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian–Eulerian approach. Valvular performance and regional leaflet wall-shear stress were quantified in terms of Valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV.
Dawn J Abbott - One of the best experts on this subject based on the ideXlab platform.
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relative costs of surgical and transcatheter Aortic Valve replacement and medical therapy
Circulation-cardiovascular Interventions, 2020Co-Authors: Andrew M Goldsweig, Hyo Jung Tak, Li Wu Chen, Herbert D Aronow, Binita Shah, Dhaval Kolte, Poonam Velagapudi, Nihar R Desai, Molly Szerlip, Dawn J AbbottAbstract:Background: The number of patients treated for Aortic Valve Disease in the United States is increasing rapidly. Transcatheter Aortic Valve replacement (TAVR) is supplanting surgical Aortic Valve re...
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the evolving management of Aortic Valve Disease 5 year trends in savr tavr and medical therapy
American Journal of Cardiology, 2019Co-Authors: Andrew M Goldsweig, Hyo Jung Tak, Li Wu Chen, Herbert D Aronow, Binita Shah, Dhaval Kolte, Poonam Velagapudi, Nihar R Desai, Molly Szerlip, Dawn J AbbottAbstract:Aortic stenosis (AS) and regurgitation (AR) may be treated with surgical Aortic Valve replacement (SAVR), transcatheter AVR (TAVR), or medical therapy (MT). Data are lacking regarding the usage of SAVR, TAVR, and MT for patients hospitalized with Aortic Valve Disease and the characteristics of the patients and hospitals associated with each therapy. From the Nationwide Readmissions Database, we determined utilization trends for SAVR, TAVR, and MT in patients with Aortic Valve Disease admitted from 2012 to 2016 for Valve replacement, heart failure, unstable angina, non-ST-elevation myocardial infarction, or syncope. We also performed multinomial logistic regressions to investigate associations between patient and hospital characteristics and treatment. Among 366,909 patients hospitalized for Aortic Valve Disease, there was a 48.1% annual increase from 2012 through 2016. Overall, 19.9%, 6.7%, and 73.4% of patients received SAVR, TAVR, and MT, respectively. SAVR decreased from 21.9% in 2012 to 18.5% in 2016, whereas TAVR increased from 2.6% to 12.5%, and MT decreased from 75.5% to 69.0%. Older age, female sex, greater severity of illness, more admission diagnoses, not-for-profit hospitals, large hospitals, and urban teaching hospitals were associated with greater use of TAVR. In multivariable analysis, likelihood of TAVR relative to SAVR increased 4.57-fold (95% confidence interval 4.21 to 4.97). TAVR has increased at the expense of both SAVR and MT, a novel finding. However, this increase in TAVR was distributed inequitably, with certain patients more likely to receive TAVR certain hospitals more likely to provide TAVR. With the expected expansion of indications, inequitable access to TAVR must be addressed.
Elena Aikawa - One of the best experts on this subject based on the ideXlab platform.
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multi omics approaches to define calcific Aortic Valve Disease pathogenesis
Circulation Research, 2021Co-Authors: Mark C Blaser, Simon Kraler, Thomas F Luscher, Elena AikawaAbstract:Calcific Aortic Valve Disease sits at the confluence of multiple world-wide epidemics of aging, obesity, diabetes, and renal dysfunction, and its prevalence is expected to nearly triple over the next 3 decades. This is of particularly dire clinical relevance, as calcific Aortic Valve Disease can progress rapidly to Aortic stenosis, heart failure, and eventually premature death. Unlike in atherosclerosis, and despite the heavy clinical toll, to date, no pharmacotherapy has proven effective to halt calcific Aortic Valve Disease progression, with invasive and costly Aortic Valve replacement representing the only treatment option currently available. This substantial gap in care is largely because of our still-limited understanding of both normal Aortic Valve biology and the key regulatory mechanisms that drive Disease initiation and progression. Drug discovery is further hampered by the inherent intricacy of the valvular microenvironment: a unique anatomic structure, a complex mixture of dynamic biomechanical forces, and diverse and multipotent cell populations collectively contributing to this currently intractable problem. One promising and rapidly evolving tactic is the application of multiomics approaches to fully define Disease pathogenesis. Herein, we summarize the application of (epi)genomics, transcriptomics, proteomics, and metabolomics to the study of valvular heart Disease. We also discuss recent forays toward the omics-based characterization of valvular (patho)biology at single-cell resolution; these efforts promise to shed new light on cellular heterogeneity in healthy and Diseased valvular tissues and represent the potential to efficaciously target and treat key cell subpopulations. Last, we discuss systems biology- and network medicine-based strategies to extract meaning, mechanisms, and prioritized drug targets from multiomics datasets.
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in vitro 3d model and mirna drug delivery to target calcific Aortic Valve Disease
Clinical Science, 2017Co-Authors: Casper Van Der Ven, Mark W Tibbitt, Alain Van Mil, Joost P G Sluijter, Robert Langer, Elena AikawaAbstract:Calcific Aortic Valve Disease (CAVD) is the most prevalent valvular heart Disease in the Western population, claiming 17000 deaths per year in the United States and affecting 25% of people older than 65 years of age. Contrary to traditional belief, CAVD is not a passive, degenerative Disease but rather a dynamic Disease, where initial cellular changes in the Valve leaflets progress into fibrotic lesions that induce Valve thickening and calcification. Advanced thickening and calcification impair Valve function and lead to Aortic stenosis (AS). Without intervention, progressive ventricular hypertrophy ensues, which ultimately results in heart failure and death. Currently, Aortic Valve replacement (AVR), surgical or transcatheter, is the only effective therapy to treat CAVD. However, these costly interventions are often delayed until the late stages of the Disease. Nonetheless, 275000 are performed per year worldwide, and this is expected to triple by 2050. Given the current landscape, next-generation therapies for CAVD are needed to improve patient outcome and quality of life. Here, we first provide a background on the Aortic Valve (AV) and the pathobiology of CAVD as well as highlight current directions and future outlook on the development of functional 3D models of CAVD in vitro . We then consider an often-overlooked aspect contributing to CAVD: miRNA (mis)regulation. Therapeutics could potentially normalize miRNA levels in the early stages of the Disease and may slow its progression or even reverse calcification. We close with a discussion of strategies that would enable the use of miRNA as a therapeutic for CAVD. This focuses on an overview of controlled delivery technologies for nucleic acid therapeutics to the Valve or other target tissues. * ABCG2, : ATP-binding cassette, sub-family G, member 2; AS, : Aortic stenosis; ASO, : antisense oligonucleotide; AV, : Aortic Valve; AVR, : Aortic Valve replacement; BAV, : bicuspid Aortic Valve; BMP-2, : bone morphogenetic protein 2; CAVD, : calcific Aortic Valve Disease; ECM, : extracellular matrix; EndMT, : endothelial-to-mesenchymal transition; ERK1/2, : extracellular signal-regulated protein kinases 1 and 2; DGCR8, : DiGeorge syndrome critical region gene 8; 2′-F, : 2′-fluoro; GelMA, : methacrylated gelatin; HAMA, : methacrylated hyaluronic acid; LDL, : low-density lipoprotein; LNA, : locked nucleic acid; LNP, : lipid nanoparticle; LRP5, : low-density lipoprotein receptor-related protein 5; 2′-MOE, : 2′- O -methoxyethyl; 2′-OMe, : 2′- O -methyl; NF-κB, : nuclear factor kappa-B; OPG, : osteoprotegerin; OTE, : off-target effects; PD/PK, : pharmacodynamics/pharmacokinetics; PEI, : polyetheleneimine; PI3K, : phosphoinositide 3-kinase; PLA, : poly(lactic acid); PLL, : poly-L-lysine; pre-miRNA, : precursor miRNA; pri-miRNA, : primary miRNA transcript; RANK, : receptor activator of nuclear factor κ-B; RANKL, : receptor activator of nuclear factor κ-B ligand; RISC, : RNA-induced silencing complex; RT-qPCR, : real-time quantitative PCR; Runx2, : runt-related transcription factor 2; α-SMA, : α-smooth muscle actin; SMAD, : similar to mothers against decapentaplegic; TGF-β1, : transforming growth factor-β 1; TNF-α, : tumour necrosis factor-α; UTMD, : ultrasound triggered microbubble destruction; VEC, : valvular endothelial cell; VIC, : Valve interstitial cell; ZEN, : N,N-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine
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potential drug targets for calcific Aortic Valve Disease
Nature Reviews Cardiology, 2014Co-Authors: Joshua D Hutcheson, Elena Aikawa, David W MerrymanAbstract:The prevalence of calcific Aortic Valve Disease (CAVD) is increasing as the global population ages. In the absence of a specific drug therapy, the only treatment for CAVD is Valve replacement. In this Review, Hutcheson et al. discuss the mechanisms of CAVD and identify potential therapeutic targets that warrant further investigation.
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calcific Aortic Valve Disease not simply a degenerative process a review and agenda for research from the national heart and lung and blood institute Aortic stenosis working group
Circulation, 2011Co-Authors: Nalini M Rajamannan, Elena Aikawa, Linda L Demer, Craig A Simmons, Patrick Mathieu, Donald D Heistad, Kristyn S Masters, Frank Evans, Jane K Grandeallen, Kevin D ObrienAbstract:Calcific Aortic Valve Disease (CAVD) encompasses the range of Disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal Valve function, is termed Aortic Valve sclerosis, but it is likely that the initiating events in the Disease process occur much earlier. Disease progression is characterized by a process of thickening of the Valve leaflets and the formation of calcium nodules – often including the formation of actual bone – and new blood vessels, which are concentrated near the Aortic surface. End stage Disease, e.g. calcific Aortic stenosis, is characterized pathologically by large nodular calcific masses within the Aortic cusps that protrude through the outflow surfaces into the sinuses of Valsalva, interfering with opening of the cusps. For decades, this Disease was thought to be a passive process in which the Valve degenerates with age in association with calcium accumulation. Moreover, although calcific Aortic Valve Disease is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated Disease process that cannot be characterized exclusively as “senile” or “degenerative.” The NHLBI convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat and potentially prevent this complex Disease process.
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calcific Aortic Valve Disease not simply a degenerative process a review and agenda for research from the national heart and lung and blood institute Aortic stenosis working group executive summary calcific Aortic Valve Disease 2011 update
Circulation, 2011Co-Authors: Nalini M Rajamannan, Elena Aikawa, Linda L Demer, Craig A Simmons, Patrick Mathieu, Donald D Heistad, Kristyn S Masters, Frank Evans, Jane K Grandeallen, Kevin D ObrienAbstract:Calcific Aortic Valve Disease (CAVD) encompasses the range of Disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal Valve function, is termed Aortic Valve sclerosis, but it is likely that the initiating events in the Disease process occur much earlier. Disease progression is characterized by a process of thickening of the Valve leaflets and the formation of calcium nodules—often including the formation of actual bone—and new blood vessels, which are concentrated near the Aortic surface. End-stage Disease, eg, calcific Aortic stenosis, is characterized pathologically by large nodular calcific masses within the Aortic cusps that protrude along the Aortic surface into the sinuses of Valsalva, interfering with opening of the cusps. There is no Disease along the ventricular surface. For decades, this Disease was thought to be a passive process in which the Valve degenerates with age in association with calcium accumulation. Moreover, although CAVD is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated Disease process that cannot be characterized exclusively as senile or degenerative. The National Heart, Lung, and Blood Institute convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat, and potentially prevent this complex Disease process. ### Key Structure-Function Correlations Heart Valves permit unobstructed, unidirectional forward flow through the circulation. …
Nalini M Rajamannan - One of the best experts on this subject based on the ideXlab platform.
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defining the role of fluid shear stress in the expression of early signaling markers for calcific Aortic Valve Disease
PLOS ONE, 2013Co-Authors: Nalini M Rajamannan, Philippe SucoskyAbstract:Calcific Aortic Valve Disease (CAVD) is an active process presumably triggered by interplays between cardiovascular risk factors, molecular signaling networks and hemodynamic cues. While earlier studies demonstrated that alterations in fluid shear stress (FSS) on the fibrosa could trigger inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. This knowledge could be critical to the elucidation of key CAVD risk factors such as congenital Valve defects, aging and hypertension, which are known to generate FSS disturbances. The objective of this study was to characterize ex vivo the contribution of isolated and combined abnormalities in FSS magnitude and frequency to early valvular pathogenesis. The ventricularis and fibrosa of porcine Aortic Valve leaflets were exposed simultaneously to different combinations of sub-physiologic/physiologic/supra-physiologic levels of FSS magnitude and frequency for 24, 48 and 72 hours in a double cone-and-plate device. Endothelial activation and paracrine signaling were investigated by measuring cell-adhesion molecule (ICAM-1, VCAM-1) and cytokine (BMP-4, TGF-β1) expressions, respectively. Extracellular matrix (ECM) degradation was characterized by measuring the expression and activity of the proteases MMP-2, MMP-9, cathepsin L and cathepsin S. The effect of the FSS treatment yielding the most significant pathological response was examined over a 72-hour period to characterize the time-dependence of FSS mechano-transduction. While cytokine expression was stimulated under elevated FSS magnitude at normal frequency, ECM degradation was stimulated under both elevated FSS magnitude at normal frequency and physiologic FSS magnitude at abnormal frequency. In contrast, combined FSS magnitude and frequency abnormalities essentially maintained valvular homeostasis. The pathological response under supra-physiologic FSS magnitude peaked at 48 hours but was then maintained until the 72-hour time point. This study confirms the sensitivity of Valve leaflets to both FSS magnitude and frequency and suggests the ability of supra-physiologic FSS levels or abnormal FSS frequencies to initiate CAVD mechanisms.
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computational assessment of bicuspid Aortic Valve wall shear stress implications for calcific Aortic Valve Disease
Biomechanics and Modeling in Mechanobiology, 2012Co-Authors: Santanu Chandra, Nalini M Rajamannan, Philippe SucoskyAbstract:The bicuspid Aortic Valve (BAV) is associated with a high prevalence of calcific Aortic Valve Disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid Aortic Valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian–Eulerian approach. Valvular performance and regional leaflet wall-shear stress were quantified in terms of Valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV.
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calcific Aortic Valve Disease not simply a degenerative process a review and agenda for research from the national heart and lung and blood institute Aortic stenosis working group
Circulation, 2011Co-Authors: Nalini M Rajamannan, Elena Aikawa, Linda L Demer, Craig A Simmons, Patrick Mathieu, Donald D Heistad, Kristyn S Masters, Frank Evans, Jane K Grandeallen, Kevin D ObrienAbstract:Calcific Aortic Valve Disease (CAVD) encompasses the range of Disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal Valve function, is termed Aortic Valve sclerosis, but it is likely that the initiating events in the Disease process occur much earlier. Disease progression is characterized by a process of thickening of the Valve leaflets and the formation of calcium nodules – often including the formation of actual bone – and new blood vessels, which are concentrated near the Aortic surface. End stage Disease, e.g. calcific Aortic stenosis, is characterized pathologically by large nodular calcific masses within the Aortic cusps that protrude through the outflow surfaces into the sinuses of Valsalva, interfering with opening of the cusps. For decades, this Disease was thought to be a passive process in which the Valve degenerates with age in association with calcium accumulation. Moreover, although calcific Aortic Valve Disease is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated Disease process that cannot be characterized exclusively as “senile” or “degenerative.” The NHLBI convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat and potentially prevent this complex Disease process.
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calcific Aortic Valve Disease not simply a degenerative process a review and agenda for research from the national heart and lung and blood institute Aortic stenosis working group executive summary calcific Aortic Valve Disease 2011 update
Circulation, 2011Co-Authors: Nalini M Rajamannan, Elena Aikawa, Linda L Demer, Craig A Simmons, Patrick Mathieu, Donald D Heistad, Kristyn S Masters, Frank Evans, Jane K Grandeallen, Kevin D ObrienAbstract:Calcific Aortic Valve Disease (CAVD) encompasses the range of Disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal Valve function, is termed Aortic Valve sclerosis, but it is likely that the initiating events in the Disease process occur much earlier. Disease progression is characterized by a process of thickening of the Valve leaflets and the formation of calcium nodules—often including the formation of actual bone—and new blood vessels, which are concentrated near the Aortic surface. End-stage Disease, eg, calcific Aortic stenosis, is characterized pathologically by large nodular calcific masses within the Aortic cusps that protrude along the Aortic surface into the sinuses of Valsalva, interfering with opening of the cusps. There is no Disease along the ventricular surface. For decades, this Disease was thought to be a passive process in which the Valve degenerates with age in association with calcium accumulation. Moreover, although CAVD is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated Disease process that cannot be characterized exclusively as senile or degenerative. The National Heart, Lung, and Blood Institute convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat, and potentially prevent this complex Disease process. ### Key Structure-Function Correlations Heart Valves permit unobstructed, unidirectional forward flow through the circulation. …
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cellular pathogenesis of degenerative valvular heart Disease from calcific Aortic stenosis to myxomatous mitral Valve Disease
2009Co-Authors: Nalini M RajamannanAbstract:INTRODUCTION HISTORICAL PERSPECTIVE OF VALVULAR HEART Disease GROSS PATHOLOGY OF Aortic Valve Disease GROSS PATHOLOGY OF MITRAL Valve Disease RISK FACTOR HYPOTHESIS FOR VALVULAR HEART Disease HYPERCHOLESTEROLEMIC Aortic Valve Disease Aortic Valve CALCIFICATION HYPERCHOLESTEROLEMIC MITRAL Valve Disease EXPERIMENTAL EFFECTS OF STATINS IN ATHEROSCLEROTIC Aortic ValveS TRANSLATIONAL THERAPEUTIC IMPLICATIONS FOR Aortic Valve Disease SUMMARY ACKNOWLEDGMENTS REFERENCES
Andrew M Goldsweig - One of the best experts on this subject based on the ideXlab platform.
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relative costs of surgical and transcatheter Aortic Valve replacement and medical therapy
Circulation-cardiovascular Interventions, 2020Co-Authors: Andrew M Goldsweig, Hyo Jung Tak, Li Wu Chen, Herbert D Aronow, Binita Shah, Dhaval Kolte, Poonam Velagapudi, Nihar R Desai, Molly Szerlip, Dawn J AbbottAbstract:Background: The number of patients treated for Aortic Valve Disease in the United States is increasing rapidly. Transcatheter Aortic Valve replacement (TAVR) is supplanting surgical Aortic Valve re...
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the evolving management of Aortic Valve Disease 5 year trends in savr tavr and medical therapy
American Journal of Cardiology, 2019Co-Authors: Andrew M Goldsweig, Hyo Jung Tak, Li Wu Chen, Herbert D Aronow, Binita Shah, Dhaval Kolte, Poonam Velagapudi, Nihar R Desai, Molly Szerlip, Dawn J AbbottAbstract:Aortic stenosis (AS) and regurgitation (AR) may be treated with surgical Aortic Valve replacement (SAVR), transcatheter AVR (TAVR), or medical therapy (MT). Data are lacking regarding the usage of SAVR, TAVR, and MT for patients hospitalized with Aortic Valve Disease and the characteristics of the patients and hospitals associated with each therapy. From the Nationwide Readmissions Database, we determined utilization trends for SAVR, TAVR, and MT in patients with Aortic Valve Disease admitted from 2012 to 2016 for Valve replacement, heart failure, unstable angina, non-ST-elevation myocardial infarction, or syncope. We also performed multinomial logistic regressions to investigate associations between patient and hospital characteristics and treatment. Among 366,909 patients hospitalized for Aortic Valve Disease, there was a 48.1% annual increase from 2012 through 2016. Overall, 19.9%, 6.7%, and 73.4% of patients received SAVR, TAVR, and MT, respectively. SAVR decreased from 21.9% in 2012 to 18.5% in 2016, whereas TAVR increased from 2.6% to 12.5%, and MT decreased from 75.5% to 69.0%. Older age, female sex, greater severity of illness, more admission diagnoses, not-for-profit hospitals, large hospitals, and urban teaching hospitals were associated with greater use of TAVR. In multivariable analysis, likelihood of TAVR relative to SAVR increased 4.57-fold (95% confidence interval 4.21 to 4.97). TAVR has increased at the expense of both SAVR and MT, a novel finding. However, this increase in TAVR was distributed inequitably, with certain patients more likely to receive TAVR certain hospitals more likely to provide TAVR. With the expected expansion of indications, inequitable access to TAVR must be addressed.