Hemodynamic Loading of the Left Ventricle and Aorta in Aortic Valve Disease

主动脉瓣疾病中左心室和主动脉的血流动力学负荷

• 批准号: 8700657
• 负责人: ALEX J. BARKER
• 金额: $ 14.65万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700657
• 关键词: Acceleration; Address; Agreement; Anatomy; Aneurysm; Aorta; Aortic Valve Insufficiency; Aortic Valve Stenosis; Architecture; Area; Blood; Blood flow; Caliber; Cardiac; Cardiac Surgery procedures; Cardiology; Cardiovascular system; Caring; Cell physiology; Cessation of life; Clinical; Clinical Sciences; Clinical Trials; Complex; Congenital Abnormality; Development; Dilatation - action; Disease; Disease Outcome; Disease Progression; EFRAC; Endothelial Cells; Enrollment; Exhibits; Extracellular Matrix; Fibrosis; Functional disorder; Geometry; Goals; Gold; Guidelines; Heart; Heart failure; Image; In Vitro; Interobserver Variability; Intervention; K-Series Research Career Programs; Lead; Left; Left Ventricular Dysfunction; Left ventricular structure; Lesion; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mentors; Methods; Metric; Mind; Molecular; Myocardial; Myocardial dysfunction; Myocardial tissue; Operative Surgical Procedures; Outcome; Outcomes Research; Pathway interactions; Patients; Pattern; Physics; Physiological; Pilot Projects; Play; Protocols documentation; Research; Research Personnel; Research Project Grants; Resected; Risk; Role; Severities; Severity of illness; Side; Source; Stenosis; Stratification; Stroke Volume; Structure; System; Testing; Time; Tissues; Training; Training Activity; Translating; Vascular remodeling; Ventricular; Ventricular Function; aortic valve; aortic valve disorder; base; bicuspid aortic valve; cardiovascular imaging; career; design; disorder risk; follow-up; hemodynamics; human subject; improved; in vivo; insight; novel; patient population; pressure; prognostic; programs; prospective; public health relevance; repaired; shear stress; standard measure

DESCRIPTION (provided by applicant): Many Aortic valve disease (AVD) such as stenosis, insufficiency, or congenital defect can severely disrupt normal function of the left ventricle (LV) and aorta. However, the role of AVD and the development of concomitant myocardial dysfunction and aortopathy are not fully understood nor sufficiently characterized. Paradoxically, it is well known that similarly classified AVD patients under the ACC/AHA guidelines can have radically divergent outcomes - implying an incomplete characterization of the disease. To address these limitations, this career development award (CDA) is designed to leverage the PI's quantitative background in fluid dynamics, imaging physics, and cardiovascular imaging in order to further understand the mechanisms leading to LV dysfunction and aortopathy with the ultimate goal to improve AVD risk stratification. The CDA will be used to further the PI's trainin in translational clinical science through formal training in Clinical Investigation and specialized mentor oversight of the research plan, specifically in the areas of cardiology, cardiac surgery, tissue characterization and cardiac standard-of-care imaging. These training activities play into the PI's career goal to become a cross-disciplinary independent investigator at the intersection of cardiovascular hemodynamics, imaging physics, and cardiovascular outcomes research. The research project proposes the development of a comprehensive MRI exam to integrate valve geometry and function with the resulting aortic hemodynamics and energetics. It will be executed according to specific aims tailored to: (1) develop and optimize a MRI protocol designed to obtain aortic valve dynamics, aortic 3D blood flow, blood acceleration fields, and thus high SNR regional wall shear stress (WSS) and energy loss measures; (2) characterize the sensitivity of the measurements in healthy and disease states using physiologic flow phantoms and in-vivo test-retest reliability; (3) perform a longitudinal patient study aimed to correlate energy loss and WSS to outcomes and disease progression in a patient population consisting of moderate to severe aortic valve stenosis subjects. These development activities form a basis for the PI to translate his fluid dynamics and cardiovascular imaging research portfolio into an independent program focusing on the need for better risk-stratification and interventional timing in AVD patients. Additionally, novel insights into the mechanistic role of flow conditions on aortopathy and LV dysfunction will be investigated.

描述（由申请人提供）：许多主动脉瓣疾病（AVD），如狭窄、关闭不全或先天性缺陷，可严重破坏左心室（LV）的正常功能 和主动脉。然而，AVD的作用以及伴随的心肌功能障碍和心肌病的发展尚未完全了解，也未充分表征。巧合的是，众所周知，根据ACC/AHA指南分类相似的AVD患者可能具有根本不同的结局-这意味着对疾病的描述不完整。为了解决这些局限性，该职业发展奖（CDA）旨在利用PI在流体动力学、成像物理学和心血管成像方面的定量背景，以进一步了解导致LV功能障碍和心血管病的机制，最终目标是改善AVD风险分层。 CDA将用于通过临床研究和专业培训， 指导监督研究计划，特别是在心脏病学、心脏外科、组织表征和心脏标准护理成像领域。这些培训活动符合PI的职业目标，即成为心血管血流动力学、成像物理学和心血管结局研究交叉领域的跨学科独立研究者。 该研究项目建议开发一种全面的MRI检查，将瓣膜几何形状和功能与所产生的主动脉血流动力学和能量学相结合。其将根据特定目标执行，以：（1）开发和优化MRI方案，旨在获得主动脉瓣动力学、主动脉3D血流、血液加速度场，从而获得高SNR区域壁剪切应力（WSS）和能量损失测量值;（2）使用生理流量模型和体内重测可靠性表征健康和疾病状态下测量值的灵敏度;（3）进行纵向患者研究，旨在将能量损失和WSS与由中度至重度主动脉瓣狭窄受试者组成的患者群体中的结果和疾病进展相关联。 这些开发活动构成了PI将其流体动力学和心血管成像研究组合转化为独立项目的基础，该项目重点关注AVD患者中更好的风险分层和介入时机的需求。此外，将研究流动条件对心脏病和LV功能障碍的机制作用的新见解。