Ventricular and Pulmonary Vascular Reserve after the Fontan Operation

项目摘要 候选人：埃贝博士的长期目标是成为成人领域的独立临床研究者 先天性心脏病他的短期目标是研究血液动力学的新的和未探索的方面， Fontan姑息治疗患者的临床结局。为了实现这些目标，埃贝博士计划：（1）收购 在先进的统计方法，运动生理学和血液动力学，以及管理的专业知识， Fontan生理学患者的循环衰竭;（2）与其他患者建立新的合作关系 研究人员;（3）在获奖的第3年和第5年提交RO 1提案。 环境：马约诊所是世界知名的创新和研究中心， 马约诊所的先天性心脏病项目为北卡罗来纳州最大的Fontan患者队列提供护理 美国，使其成为拟议研究招募患者的理想选择。Borlaug博士， 他是运动血液动力学和心血管生理学方面的专家， 成功的指导。 研究 背景：由于Fontan，Fontan姑息治疗患者的长期生存率显著降低 相关疾病（FAD）。现有数据表明，FAD是慢性静脉曲张的下游并发症， 充血，但缺乏关于上游血流动力学过程的数据，如肺动脉高压。 血管疾病（PVD）和心室舒张功能障碍（VDD），导致慢性静脉充血 和FAD。我们将通过拟议的研究解决这些知识差距。 具体目的：我们将使用以下方法确定Fontan生理学患者的PVD和VDD患病率： 有创和无创血流动力学心肺运动试验（目的#1和#2），然后评价 静息-运动PVD和VDD对临床结局的影响（目标3）。 研究设计和结果测量：研究将在接受Fontan治疗的成人患者中进行。 马约诊所罗切斯特，明尼苏达州的临床适应症的心脏导管插入术。同时心脏 将在休息和运动时进行导管插入术和超声心动图检查（目标1和2）， 静息-运动PVD和VDD的发生将与随访期间的临床结局相关（目标3）。 潜在的公共卫生贡献：识别和治疗PVD和VDD的早期阶段， 潜在地预防或至少阻止FAD，提高存活率并降低该人群的医疗费用。 与候选人职业目标的关系：在这些项目中获得的数据和技能将 形成了RO 1应用的基础，重点是修改FAD的自然历史，这是实现 成为该领域的独立临床研究者。

PROJECT SUMMARY CANDIDATE: Dr. Egbe's long-term goal is to become an independent clinical investigator in the field of adult congenital heart disease. His short-term goal is to study new and unexplored aspects of hemodynamics and clinical outcomes in people with Fontan palliation. To achieve these goals, Dr. Egbe plans to: (1) Acquire expertise in advanced statistical methodology, exercise physiology and hemodynamics, and management of circulatory failure in people with Fontan physiology; (2) Develop new collaborative relationships with other researchers; (3) Submit RO1 proposals during the 3rd and 5th years of the award. ENVIRONMENT: The Mayo Clinic is a world-renowned center for innovation and research, and the Adult Congenital Heart Disease program at Mayo Clinic cares for the largest cohort of Fontan patients in North America, making it ideal for patient recruitment for the proposed studies. Dr. Borlaug, the primary mentor for this grant, is an expert in exercise hemodynamics and cardiovascular physiology, and has a track record of successful mentorship. RESEARCH Background: Patients with Fontan palliation have significantly reduced long-term survival because of Fontan associated diseases (FAD). Available data suggest that FAD are downstream complications of chronic venous congestion, but there is paucity of data about the upstream hemodynamic processes, such as pulmonary vascular disease (PVD) and ventricular diastolic dysfunction (VDD), responsible for chronic venous congestion and FAD. We will address these gaps in knowledge through the proposed studies. Specific Aims: We will determine the prevalence of PVD and VDD in patients with Fontan physiology using invasive and noninvasive hemodynamic cardiopulmonary exercise testing (Aims #1 and #2), and then evaluate the impact of rest-exercise PVD and VDD on clinical outcomes (Aim #3). Study Design and Outcome Measures: The studies will be conducted on adult Fontan patients undergoing cardiac catheterization for clinical indications at Mayo Clinic Rochester, MN. Simultaneous cardiac catheterization and echocardiography will be performed at rest and during exercise (Aims #1 and #2), and the occurrence of rest-exercise PVD and VDD will be correlated with clinical outcomes during follow-up (Aim#3). Potential Public Health Contribution: Identifying and treating the early stages of PVD and VDD will potentially prevent or at least deter FAD, improve survival and reduce healthcare cost in this population. Relationship to the Career Goals of the Candidate: The data and skill set acquired during these projects will form the basis for an RO1 application focused on modifying the natural history of FAD, a critical step towards becoming an independent clinical investigator in this field.