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），例如狭窄，不足或先天性缺陷会严重破坏左心室（LV）的正常功能 和主动脉。但是，AVD的作用以及伴随的心肌功能障碍和主动脉症的发展尚未完全理解或充分表征。矛盾的是，众所周知，根据ACC/AHA准则，类似分类的AVD患者可以产生根本不同的结果 - 这意味着对疾病的表征不完整。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，以便进一步了解导致LV功能障碍和主动脉疾病的机制，并具有最终的目标，以改善AVD风险分层。 CDA将通过临床研究和专业的正式培训来进一步推动PI的转化临床科学培训 对研究计划的指导监督，特别是心脏病学，心脏手术，组织表征和心脏标准成像领域。这些培训活动在PI的职业目标中发挥了作用，成为心血管血流动力学，成像物理学和心血管成果研究的交集的跨学科独立研究者。 该研究项目提出了一项全面的MRI检查，以将阀几何形状和功能与所得的主动脉血流动力学和能量学结合起来。它将根据量身定制的特定目的进行执行：（1）开发和优化旨在获得主动脉瓣动力学，主动脉3D血流，血液加速度场以及因此高SNR区域壁剪应力（WSS）和能量损失措施的MRI方案； （2）使用生理流幻象和体内测试 - 重测可靠性来表征健康和疾病状态中测量的敏感性； （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人群的结局和疾病进展相关联。 这些开发活动构成了PI将其流体动力和心血管成像研究组合转化为一个独立计划的基础，该计划着重于在AVD患者中需要更好的风险分层和介入时间。此外，将研究对流动条件对主动脉疾病和LV功能障碍的机械作用的新见解。