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Arteriosclerosis, Thrombosis, and... Apr 2020Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic... (Review)
Review
Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.
Topics: Animals; Aortic Valve Stenosis; Cell Communication; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular; Humans; Inflammation; Lipoproteins; Myofibroblasts; Osteoblasts; Osteoclasts; RNA, Untranslated; Vascular Calcification
PubMed: 32160774
DOI: 10.1161/ATVBAHA.119.313067 -
Circulation Research Apr 2021Calcific aortic valve disease sits at the confluence of multiple world-wide epidemics of aging, obesity, diabetes, and renal dysfunction, and its prevalence is expected... (Review)
Review
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.
Topics: Aortic Valve; Aortic Valve Stenosis; Biomechanical Phenomena; Calcinosis; Computational Biology; Disease Progression; Drug Discovery; Epigenesis, Genetic; Gene Expression; Genomics; Heart Failure; Humans; Mass Spectrometry; Medical Illustration; Metabolomics; Phenotype; Proteomics; Transcatheter Aortic Valve Replacement; Transcriptome
PubMed: 33914608
DOI: 10.1161/CIRCRESAHA.120.317979 -
JACC. Cardiovascular Interventions Aug 2022
Topics: Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Risk Factors; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 35981842
DOI: 10.1016/j.jcin.2022.07.003 -
Heart Failure Reviews Sep 2023Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the... (Review)
Review
Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management.
Topics: Humans; Quality of Life; Balloon Valvuloplasty; Aortic Valve Stenosis; Aortic Valve; Heart Valve Prosthesis; Heart Failure; Treatment Outcome
PubMed: 37083966
DOI: 10.1007/s10741-023-10312-7 -
JACC. Cardiovascular Interventions Nov 2021
Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34756540
DOI: 10.1016/j.jcin.2021.09.005 -
JACC. Cardiovascular Interventions Jun 2021
Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Hemodynamics; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34112459
DOI: 10.1016/j.jcin.2021.04.024 -
JACC. Cardiovascular Imaging Feb 2020
Topics: Aortic Valve Stenosis; Fibrosis; Humans; Myocardium
PubMed: 31326482
DOI: 10.1016/j.jcmg.2019.05.021 -
The Journal of Thoracic and... Apr 2021
Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Simvastatin; Transcatheter Aortic Valve Replacement
PubMed: 31813536
DOI: 10.1016/j.jtcvs.2019.10.138 -
Journal of the American College of... Oct 2022
Topics: Humans; Hypertension, Pulmonary; Aortic Valve Stenosis; Transcatheter Aortic Valve Replacement; Aortic Valve; Treatment Outcome; Risk Factors; Heart Valve Prosthesis
PubMed: 36265956
DOI: 10.1016/j.jacc.2022.09.005 -
Journal of the American College of... Jun 2021
Topics: Aortic Valve Stenosis; Humans; Stroke Volume
PubMed: 34082910
DOI: 10.1016/j.jacc.2021.04.027