Acute Imposition of Fontan Physiology in The Single Ventricle Patient: Effects on Fibrosis, Function and Drug Intervention

项目摘要/摘要 先天性心脏病(CHD)并发0.8-1%的活产儿，是#年主要的死亡原因之一。 孩子们。那些出生时只有一个泵室，即单个脑室(SV)的人，最容易发病和 死亡率，消耗了大量和不成比例的医疗资源。这些婴儿存活到 在一系列姑息性心脏手术后成年，最终在丰坦手术中达到高潮。近85%的 那些接受丰坦手术的人在手术后活了30年，估计有6万人 活在今天的病人。不幸的是，他们遭受了多种并发症，如肝纤维化，淋巴管 充血和蛋白质丢失肠病，仅举几例。此外，青光眼独特的病理生理学 Fontan循环本身可能会导致心脏纤维化和衰竭，原因有很多(例如一个泵室 执行两个人的工作)。虽然描述临床状态的研究正在年龄较大的儿童和 对于年轻人来说，这些并发症的发病原因尚不清楚。这项提议试图填补的知识缺口 正在了解肝和心脏纤维化的起点以及淋巴异常以及 通过在实施方丹之前和之后相对较早地评估这些因素，来评估它们之间的相互作用 发行量。此外，还将进行抗纤维化药物螺内酯的试点试验，以确定是否 这种方法可以减少纤维化，如果磁共振成像(MRI)能够识别这种差异。 本研究的目的是通过非侵入性手段描述急性心肌梗死后肝纤维化的后果。 应用Fontan血流动力学，并研究肝和心脏纤维化之间的相互关系， 血流动力学异常和淋巴充血。螺内酯的试点试验将确定 从机制上讲，它是否可以减轻SV患者的纤维化，以及MRI是否能区分这种差异。这个 血清生物标记物和MRI的结合形成了一种强大的非侵入性工具 器官功能障碍的复杂网络。在方坦手术后的一年、两年甚至可能是三年前， 儿童将接受核磁共振检查，以评估肝和心脏纤维化、心功能、血流和淋巴管。 评估。我们将探讨所有这些指标之间的相互关系。 现在方坦的死亡率在过去20年里已经显著下降，当务之急是 研究纤维性侮辱以改善一生的幸福感。这项研究具有重要意义，因为它 旨在了解如何在这些儿童进入成年后通过欣赏 Fontan血流动力学的施加在其早期阶段是如何发挥作用的，以及对 给予螺内酯对这一生理学的影响，确定核磁共振是否能分辨出这种差异。

Project Summary/Abstract Congenital heart disease (CHD) complicates 0.8–1% of live births and is one of leading causes of death in children. Those born with only one pumping chamber, a single ventricle (SV), are most prone to morbidity and mortality, consuming a significant and disproportionate amount of medical resources. These infants survive to adulthood following a series of palliative heart operations culminating in the Fontan operation. Nearly 85% of those undergoing the Fontan operation are alive up to 30 years after surgery with an estimated 60,000 such patients living today. Unfortunately, they suffer multiple complications such as liver fibrosis, lymphatic congestion and protein loosing enteropathy to name a few. In addition, the unique pathophysiology of the Fontan circulation may itself cause cardiac fibrosis and failure for many reasons (eg one pumping chamber performing the work of two). While studies describing the clinical state are taking place in older children and young adults, the onset of these complications remains unclear. The knowledge gap this proposal seeks to fill is understanding the starting point of liver and cardiac fibrosis as well as lymphatic abnormalities along with the interplay between them by assessing these before as well as relatively early after imposition of the Fontan circulation. In addition, a pilot trial of the antifibrotic agent spironolactone will be undertaken to determine if this approach could decrease fibrosis and if magnetic resonance imaging (MRI) can discern this difference. The purpose of this study is to characterize by non-invasive means the fibrotic consequences of the acute imposition of Fontan hemodynamics, and to investigate the interrelationship between liver and cardiac fibrosis, abnormal hemodynamics and lymphatic congestion. The pilot trial of spironolactone will determine mechanistically whether it can mitigate fibrosis in SV patients and if MRI can discern this difference. The combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together the complicated web of organ dysfunction. Prior to, one, two and possibly three years after Fontan operation, children will undergo MRI to assess liver and cardiac fibrosis, ventricular function and flows and lymphatic assessment. The interrelationship between all these metrics will be explored. Now that Fontan mortality has markedly decreased over the past 20 years, it’s imperative to investigate fibrotic insults in order to improve lifelong well-being. This study is significant because it aims to understand how to alleviate morbidity as these children enter their adult years by appreciating how the imposition of Fontan hemodynamics plays a role in its earliest stage and the effects of spironolactone administration on this physiology, determining if MRI can discern this difference.