Correlating Aortic Valve Structure to Heart Sound Characteristic

将主动脉瓣结构与心音特征相关联

• 批准号: 10328486
• 负责人: Valentina Dargam
• 金额: $ 3.7万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-07 至 2023-09-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328486
• 关键词: Acoustics; Address; Aortic Valve Stenosis; Apolipoprotein E; Biomechanics; Blood; Cardiac; Characteristics; Collagen Fiber; Development; Diagnosis; Diet; Disease; Disease Management; Disease Progression; Early Intervention; Elastin Fiber; Evolution; Extracellular Matrix; Fellowship; Fiber; Frequencies; Future; Goals; Hearing; Heart Sounds; Heart failure; Histologic; Image; Imaging Techniques; Intervention; Lead; Left; Measurement; Measures; Membrane; Methods; Microscopic; Minerals; Morbidity - disease rate; Mus; Nodule; Operative Surgical Procedures; Outcome; Patients; Performance; Physical Examination; Play; Prognosis; Property; Regulation; Research; Risk; Role; Sampling; Silicon; Specialist; Stethoscopes; Structure; Surface; Symptoms; Techniques; Testing; Thick; Time; Tissues; Work; aortic valve; aortic valve disorder; calcification; digital; discrete time; insight; mortality; mouse model; noninvasive diagnosis; novel; response; screening; sound; sound frequency; tool; valve replacement; vibration; vocal cord

Summary/Abstract: Aortic valve disease (AVD) occurs when aortic valve leaflets become thickened and stiff due to fibrotic remodeling and formation of calcific nodules. Consequently, aortic stenosis develops when blood distribution to the body is compromised due to the valve not being able open properly. Underdiagnosis of patients remains a problem because—even when severe—AVD can be asymptomatic. Asymptomatic patients are not referred to specialists for advanced imaging procedures that can diagnose AVD. Delayed intervention of aortic stenosis leads to cardiac remodeling and eventually cardiac failure. In order to address problems associated with underdiagnosis, screening strategies that can be implemented into routine physical examinations are needed to detect AVD in asymptomatic patients. The vibrations of aortic valve leaflets during valve closure produce the audible frequencies (S2 sound) heard through a doctor's stethoscope. We hypothesize that microstructural differences in aortic valve remodeling and related alterations in biomechanics can be identified by changes in the valvular acoustic characteristics (S2 sound) in early AVD. Structural and composition changes in the extracellular matrix (ECM) lead to the biomechanical alterations that cause AVD. The goals of the proposed study, tested through two aims, is to identify how changes in aortic valve biomechanics influence heart sound characteristics. Aim 1 will identify whether ECM structural alterations induce changes in S2 sound frequency and time characteristics in a mouse model of aortic stenosis. Aim 2 will further develop a new technique to analyze mouse aortic valve biomechanics, providing new insight into the microstructural and functional leaflet alterations during various AVD stages. The outcomes of the proposed research can contribute to the future development of a non-invasive diagnostic tool to identify patients who are at risk of developing or have severe but asymptomatic AVD. This work could have a major impact in AVD management in two ways: 1) enable identification of patients in early, reversible disease stages, enabling opportunities to explore new non-invasive treatments, and 2) diagnose asymptomatic patients with late-stage AVD, leading to lifesaving valve replacement surgery.

总结/摘要： 主动脉瓣疾病（AVD）发生在主动脉瓣小叶由于纤维化而变得增厚和僵硬时。 重塑和钙化结节的形成。因此，主动脉瓣狭窄发展时，血液分布， 由于阀不能正确地打开，主体受到损害。对患者的诊断不足仍然是一个 问题是，即使是严重的AVD也可能无症状。无症状患者不转诊 高级成像程序的专家，可以诊断AVD。主动脉瓣狭窄延迟介入治疗 导致心脏重塑最终导致心力衰竭为了解决与以下方面有关的问题， 诊断不足，需要在常规体检中实施筛查策略， 在无症状患者中检测AVD。主动脉瓣瓣叶在瓣膜闭合期间的振动产生 通过医生的听诊器听到的可听频率（S2声音）。我们假设微观结构 主动脉瓣重塑的差异和生物力学的相关改变可以通过 早期AVD的瓣膜声学特征（S2音）。结构和组成的变化 细胞外基质（ECM）导致生物力学改变，导致AVD。拟议的目标 通过两个目的进行测试的研究是确定主动脉瓣生物力学的变化如何影响心音 特色目的1将确定ECM结构改变是否诱导S2声音频率的变化， 主动脉瓣狭窄小鼠模型的时间特性。目标2将进一步开发一种新的技术来分析 小鼠主动脉瓣生物力学，为微结构和功能性瓣叶改变提供了新的见解 在不同的AVD阶段。拟议研究的结果可以有助于未来的发展， 一种非侵入性诊断工具，用于识别有发展风险或患有严重但无症状的患者 AVD.这项工作可能在两个方面对AVD管理产生重大影响：1）能够识别患者 在早期，可逆的疾病阶段，使探索新的非侵入性治疗的机会，和2） 诊断晚期AVD的无症状患者，从而进行挽救生命的瓣膜置换手术。