School of Medicine, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK.
Department of Cardiology, Northumbria Healthcare NHS Foundation Trust, North Shields, UK.
Open Heart. 2023 Mar;10(1). doi: 10.1136/openhrt-2022-002244.
Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the condition's mechanistic underpinning has shifted the paradigm to an active disease process. This advancement from the 'wear and tear' model is a result of the growing economic and health burden of AS, particularly within industrialised countries, prompting further research. 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.There is an unmet clinical need for asymptomatic patient management; no pharmacotherapies are proven to slow progression and intervention timing varies. Novel approaches are developing to address this through: (1) screening with circulating biomarkers; (2) development of drugs to slow disease progression and (3) early valve intervention guided by medical imaging. Existing biomarkers (troponin and brain natriuretic peptide) are non-specific, but cost-effective predictors of ventricular dysfunction. In addition, their integration with cardiovascular MRI can provide accurate risk stratification, aiding aortic valve replacement decision making. Currently, invasive intervention is the only treatment for AS. In comparison, the development of lipoprotein(a) lowering therapies could provide an alternative; slowing progression of CAS, preventing left ventricular dysfunction and reducing reliance on surgical intervention.The landscape of AS management is rapidly evolving. This review outlines current understanding of the pathophysiology of AS, its management and future perspectives for the condition's assessment and treatment.
我们对主动脉瓣狭窄(AS)的认识正在发生变化。从传统的被动退行性疾病观念出发,对该疾病发病机制的深入理解已经将其从一种被动退行性疾病转变为一种主动疾病过程。这种从“磨损”模型到“主动疾病过程”的转变,是由于 AS 在经济和健康方面的负担不断增加,尤其是在工业化国家,促使人们进一步开展相关研究。钙化性主动脉瓣狭窄(CAS)的病理生理学非常复杂,但可以与动脉粥样硬化的病理生理学类似。进行性重塑涉及脂质-蛋白复合物,脂蛋白(a)对于诊断和潜在的未来治疗选择特别重要。无症状患者的管理存在未满足的临床需求;没有药物被证明可以减缓疾病进展,干预时机也各不相同。为了解决这一问题,正在开发新的方法,包括:(1)使用循环生物标志物进行筛查;(2)开发减缓疾病进展的药物;(3)通过医学影像学指导早期瓣膜干预。现有的生物标志物(肌钙蛋白和脑钠肽)虽然是非特异性的,但对于预测心室功能障碍具有成本效益。此外,将其与心血管 MRI 相结合可以提供准确的风险分层,有助于主动脉瓣置换决策。目前,AS 的治疗方法主要是介入治疗。相比之下,脂蛋白(a)降低疗法的发展可能是一种替代方法;它可以减缓 CAS 的进展,防止左心室功能障碍,并减少对手术干预的依赖。AS 管理领域正在迅速发展。本文概述了目前对 AS 病理生理学、其管理以及未来评估和治疗方法的理解。
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