Understanding mechanisms of Fontan failure and key predictors for patient outcome

了解 Fontan 失败的机制和患者预后的关键预测因素

• 批准号: 8213473
• 负责人: AJIT P YOGANATHAN
• 金额: $ 74.42万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213473
• 关键词: Anatomy; Arrhythmia; Arteriovenous malformation; Automobile Driving; Award; Biomedical Engineering; Birth; Blood Circulation; Cardiac; Cardiac Output; Cardiovascular Physiology; Cardiovascular system; Case Report Form; Child; Childhood; Chronic; Clinical; Clinical Management; Clinical Markers; Cohort Analysis; Cohort Studies; Collection; Common Ventricle; Complement; Complex; Congenital Heart Defects; Cross-Sectional Studies; Data; Data Set; Databases; Dependence; Deterioration; Development; Diagnosis; Early Diagnosis; Enrollment; Environment; Equipment and supply inventories; Evaluation; Evolution; Exercise; Exercise stress test; Failure; Figs - dietary; Future; Grant; Growth; Heart Atrium; Heart failure; Hepatic; Image; Incidence; Interdisciplinary Study; Investigation; Lead; Longitudinal Studies; Lung; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Mechanics; Medical; Medical Records; Metabolic; Metric; Modeling; Myocardial dysfunction; Operative Surgical Procedures; Outcome; Output; Patients; Pediatric Hospitals; Performance; Philadelphia; Physiology; Protein-Losing Enteropathies; Protocols documentation; Pulmonary Circulation; Pulmonary Vascular Resistance; Pulmonary artery structure; Pump; Quality of life; Questionnaires; Records; Recruitment Activity; Research; Research Personnel; Resistance; Rest; Role; Sample Size; Series; Surgical Management; Testing; Time; United States National Institutes of Health; Venous; Ventricular; Ventricular Dysfunction; Ventricular Function; Work; Workload; analytical tool; cohort; design; experience; follow-up; hemodynamics; improved; in vivo; indexing; interest; longitudinal analysis; meetings; multidisciplinary; novel; outcome forecast; palliative; patient population; prevent; public health relevance; repaired

DESCRIPTION (provided by applicant): Single ventricle heart defects, where systemic and pulmonary venous returns mix in the single functional ventricle, represent the most complex form of congenital heart defect. Surgical repairs, termed "Fontan Repairs," reroute the systemic venous return directly to the pulmonary arteries, thus preventing venous return mixing and restoring normal oxygenation saturation levels. Unfortunately, these repairs are only palliative and Fontan patients are subjected to a multitude of chronic complications. Over the past 20 years, researchers have sought to understand the hemodynamics through this surgical construct in an effort to optimize its efficiency and minimize the imposed workload on the single ventricle. While this work has led to important advances in the surgical approach, including the development of the total cavopulmonary connection (TCPC), an integrated experimental and clinical approach relating these quantitative markers to ultimate patient outcomes has been lacking. Such a study would represent a critical step in the advancement of treatment efforts as it will identify the clinical markers that control outcomes, and elucidate the mechanisms of Fontan failure. Understanding these interconnections would also provide the means to develop optimal medical strategies to improve those outcomes. Therefore, the objective of this grant is to investigate the relationship between TCPC hemodynamics and ventricular function, and subsequently determine how those parameters impact patient quality of life (QOL). To achieve these objectives, the PI has assembled a multidisciplinary research team with a proven track record in the field, a novel set of established analytical tools, and the largest collection of single ventricle anatomy and flow data in the world. These assets will be utilized through the following synergistic approach: (1) we will perform a longitudinal analysis of TCPC hemodynamics and ventricular function; (2) we will compare the dynamics of the single ventricle and TCPC between rest and exercise using a CMR exercise protocol; and (3) we will conduct a cross-sectional assessment of patient QOL to quantify clinical outcomes, relate them to the measured hemodynamic and functional parameters, and determine which parameters are critical determinants and predictors of QOL. The novel components of this approach include the use of a CMR-compatible bike to obtain patient hemodynamic and function data under both resting and exercise conditions; the systematic quantification of TCPC hemodynamic (e.g. power loss) and cardiovascular function at rest and exercise in a cross-sectional study of over 150 patients; and the characterization of their temporal evolution in a longitudinal study. Correlation of these surrogates to quality of life measures will identify the strongest outcome predictors to be used for patient diagnosis. In parallel, combining these predictors with the simple mechanistic approaches will point to the cause of the deteriorating patient outcome. This will in turn help design improved surgical and clinical management strategies. PUBLIC HEALTH RELEVANCE: This grant investigates the relationship between Fontan hemodynamics and ventricular function in patients born with single-ventricle heart defects. These surrogates will subsequently be correlated to quality of life measures to identify the strongest outcome predictors to be used for patient diagnosis. Understanding these interconnections will provide the means to develop optimal medical strategies to improve those outcomes.

描述（由申请人提供）：单心室心脏缺陷，其中体静脉和肺静脉回流混合在单个功能性心室中，代表了最复杂的先天性心脏缺陷形式。手术修复，称为“Fontan修复”，将体静脉回流直接改道至肺动脉，从而防止静脉回流混合并恢复正常的氧合饱和度水平。不幸的是，这些修复只是姑息性的，Fontan患者遭受多种慢性并发症。在过去的20年里，研究人员一直试图通过这种手术结构来了解血液动力学，以优化其效率并最大限度地减少单心室的工作负荷。虽然这项工作导致了手术方法的重要进展，包括全腔静脉连接（TCPC）的发展，但缺乏将这些定量标志物与最终患者结局联系起来的综合实验和临床方法。这样的研究将代表治疗努力进步的关键一步，因为它将确定控制结果的临床标志物，并阐明Fontan失败的机制。了解这些相互联系也将提供制定最佳医疗策略以改善这些结果的方法。因此，本研究的目的是研究TCPC血流动力学与心室功能之间的关系，并随后确定这些参数如何影响患者的生活质量（QOL）。为了实现这些目标，PI组建了一支多学科研究团队，该团队在该领域拥有良好的业绩记录、一套新颖的成熟分析工具以及世界上最大的单心室解剖和流量数据集。这些资产将通过以下协同方法来利用：（1）我们将对TCPC血流动力学和心室功能进行纵向分析;（2）我们将使用CMR运动方案比较休息和运动之间的单心室和TCPC的动力学;以及（3）我们将对患者QOL进行横断面评估，以量化临床结局，将其与测量的血流动力学和功能参数相关联，并确定哪些参数是QOL的关键决定因素和预测因素。该方法的新组件包括使用CMR兼容自行车在静息和运动条件下获得患者血流动力学和功能数据;在150多名患者的横断面研究中系统量化TCPC血流动力学（例如功率损失）和静息和运动时的心血管功能;以及在纵向研究中表征其时间演变。这些替代指标与生活质量指标的相关性将确定用于患者诊断的最强结果预测因子。同时，将这些预测因素与简单的机械方法相结合，将指出患者预后恶化的原因。这反过来将有助于设计改进的手术和临床管理策略。 公共卫生关系：该基金旨在研究单心室先天性心脏病患者的Fontan血流动力学与心室功能之间的关系。这些替代物随后将与生活质量测量相关，以确定用于患者诊断的最强结果预测因子。了解这些相互联系将提供制定最佳医疗策略以改善这些结果的方法。