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: 7765241
• 负责人: AJIT P YOGANATHAN
• 金额: $ 77.49万
• 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/7765241
• 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; 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; 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）：单个心室心脏缺陷，其中全身和肺静脉回流混合在单个功能性脑室中，代表了先天性心脏缺陷的最复杂形式。手术修理，称为“ fontan修复”，将系统性静脉恢复直接恢复到肺动脉，从而防止静脉回流混合并恢复正常的氧合饱和度。不幸的是，这些维修仅是姑息性的，而方坦患者则遭受多种慢性并发症。在过去的20年中，研究人员试图通过这种外科手术结构来理解血液动力学，以优化其效率并最大程度地减少单个心室上施加的工作量。尽管这项工作导致了手术方法的重要进展，但包括总Cavopulonary Connection（TCPC）的发展，但缺乏将这些定量标记与最终患者结局相关的综合实验和临床方法。这样的研究将是治疗工作进步的关键步骤，因为它将确定控制结果的临床标志物，并阐明方坦衰竭的机制。了解这些互连还将提供一种制定最佳医疗策略以改善这些结果的方法。因此，该赠款的目的是研究TCPC血液动力学和心室功能之间的关系，然后确定这些参数如何影响患者生活质量（QOL）。为了实现这些目标，PI组装了一个具有良好的往绩记录的多学科研究团队，一组新型的已建立分析工具以及最大的单个心室解剖结构和世界上流动数据的收集。这些资产将通过以下协同方法来利用：（1）我们将对TCPC血液动力学和心室功能进行纵向分析； （2）我们将使用CMR练习方案在休息和运动之间比较单个心室和TCPC的动力学； （3）我们将对患者QOL进行横断面评估，以量化临床结果，将它们与测量的血液动力学和功能参数联系起来，并确定哪些参数是QOL的关键决定因素和预测因素。这种方法的新成分包括使用与CMR兼容的自行车在静止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，在休息时进行了TCPC血液动力学（例如功率损失）和心血管功能的系统定量；以及在纵向研究中其时间进化的表征。这些替代物与生活质量措施的相关性将确定用于患者诊断的最强结果预测因子。同时，将这些预测因子与简单的机械方法结合起来将指出导致患者预后恶化的原因。反过来，这将有助于设计改进手术和临床管理策略。 公共卫生相关性：该赠款研究了患有单腹膜心脏缺陷的患者方坦血液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措施相关，以确定用于诊断患者的最强结果预测因子。了解这些互连将为制定最佳医疗策略以改善这些结果提供手段。