The Effect of Peak Exercise on Cardiac Mechanics in patients with Single Ventricle after the Fontan Operation

项目总结/摘要 以其中一个心室（所谓的单心室）严重发育不全为特征的先天性心脏缺陷 与生命不相容，特别是当肺部或全身血流严重阻塞时。 由于采取了一系列姑息性手术将单心室转变为“系统心室”， 成千上万的病人已经活过了童年。最后一种手术，Fontan手术， 其特征在于将静脉血液从上半身和下半身直接回流到肺动脉 在没有肺下心室的情况下虽然Fontan患者现在已经进入成年早期， 由于心脏缺陷都是致命的，他们的发病率和早期死亡率很高，并且呈渐进性 运动能力和功能能力下降以及与心力衰竭相关的早期死亡， Fontan生理学相关并发症。收缩储备的关系，或增加的能力， 压力下的心室功能和运动能力在这些患者中尚不清楚。大多数研究 研究运动能力和心室功能之间的关系已经使用了静息，负荷依赖性 超声心动图指标的功能，并使用药物压力，而不是体育锻炼。一 新技术斑点追踪超声心动图通过心肌评估心脏力学 变形或应变。应变是收缩性的敏感的、相对负荷独立的量度，被认为是 在泵功能的常规测量（例如射血分数）明显变化之前，可以看到异常。 因此，应变可能是一个更有用的措施，以评估心室功能。 这项建议的总体目标是检查患者在静息和峰值运动时的心脏力学， Fontan操作及其与运动表现测量的关联。为了实现这一目标， 我们建议对60名接受心肺运动测试的受试者进行前瞻性试点研究， 在休息和运动高峰时进行超声心动图检查。在目标1中，我们将确定从静止到峰值的变化 使用应变进行心室功能（称为收缩储备）的锻炼，以及跨室梯度， 当存在时，测量为平均Fontan开窗梯度。在目标2中，我们将建立 在同一患者群体中，收缩储备与运动表现测量的相关性。 本研究将深入了解Fontan后患者的心室收缩力/对运动的反应 操作虽然Fontan患者运动表现的决定因素是多因素的，但我们认为， 研究将告知静息时收缩力减弱或收缩储备受损是否与 不依赖于其他因素的运动能力异常测量。这些结果可能会告诉我们 在这个人群中的治疗策略。完成这项研究将使Bhatt博士能够通过以下方式发展她的技能： 以指导的方式使用非侵入性成像工具进行面向患者的研究，并将提供 获得（K23）职业发展奖的初步数据，促进她走向独立。

Project Summary/Abstract Congenital heart defects characterized by severe hypoplasia of one of the ventricles (so-called single ventricles) are not compatible with life, particularly when there is severe obstruction to pulmonary or systemic blood flow. Thanks to a series of palliative procedures undertaken to convert the single ventricle into the “systemic ventricle”, thousands of patients have survived beyond childhood. The last of such procedures, the Fontan operation, is characterized by diverting venous blood return from the upper and lower body directly into the pulmonary arteries in the absence of a subpulmonary ventricle. Although Fontan patients are now reaching early adulthood with a heart defect that was uniformly fatal, they experience substantial morbidity and early mortality, with progressive decline in exercise performance and functional capacity as well as early death related to heart failure and complications related to Fontan physiology. The relationship of contractile reserve, or the ability to augment ventricular function under stress, and exercise capacity is not well understood in these patients. Most studies examining the association between exercise capacity and ventricular function have used resting, load-dependent echocardiographic indices of function and have used pharmacologic stress rather than physical exercise. A newer technique speckle tracking echocardiography assesses cardiac mechanics through myocardial deformation, or strain. Strain is a sensitive, relatively load independent measure of contractility thought to be abnormal before overt changes in conventional measures of pump function, such as ejection fraction, are seen. Therefore, strain might be a more useful measure to assess ventricular function. The overall goal of this proposal is to examine the cardiac mechanics at rest and peak exercise in patients after the Fontan operation and its association with measures of exercise performance. To accomplish this objective, we propose a prospective pilot study of 60 subjects undergoing cardiopulmonary exercise testing that will undergo echocardiogram at rest and at peak exercise. In Aim 1 we will determine the changes from rest to peak exercise in ventricular function (called contractile reserve) using strain, and the transpulmonary gradient, measured as the mean Fontan fenestration gradient when one is present. In Aim 2, we will establish the association of contractile reserve with measures of exercise performance in the same patient population. This study will provide insight into the ventricular contractility/response to exercise in patients after Fontan operation. While the determinants of exercise performance in Fontan patients are multifactorial, we believe this study will inform whether diminished contractility at rest or impaired contractile reserve are associated with abnormal measures of exercise capacity independently of other factors. These results could potentially inform therapeutic strategies in this population. Completion of this study will allow Dr. Bhatt to develop her skills by conducting patient-oriented research using non-invasive imaging tools in a mentored fashion and will provide preliminary data for a (K23) Career Development Award, fostering her development towards independence.