RE-ENERGIZE FONTAN - RandomizEd Exercise INtERvention desiGned to MaximIZE Fitness in Pediatric FONTAN patients

项目总结 超过新生儿期的单心室(“半个心脏”)儿童的存活率显著增加。 以及上演的方坦姑息疗法。然而，长期发病率仍然很高。到40岁时，50%的方坦患者 可能已经死亡或接受了心脏移植。在美国，每年有1000例方坦姑息手术， 有越来越多的方坦患者面临进行性心力衰竭和死亡的风险。影响因素 对Fontan患者心力衰竭的发生和发展的作用仍不完全清楚。然而， 现已证实，Fontan患者运动能力较差，与发病和 死亡率，除肌肉质量下降、肌肉功能异常和内皮功能障碍外 导致疾病进展的因素。在患有两个脑室和心力衰竭的成人患者中，减少运动 能力、肌肉质量和肌肉力量是不良结果和锻炼的有力预测因素 干预不仅可以提高运动能力和肌肉质量，还可以逆转内皮功能障碍。 对先天性心脏病儿童进行有限的运动干预已证明运动是安全的 而且有效；然而，这些研究都是在小而不同的群体中进行的，而且大多数都很少 方坦病人。此外，这些干预措施都没有研究运动对肌肉质量的影响 或线粒体功能，或内皮功能。我们提出了一种里程碑驱动的随机控制 在儿科Fontan患者中进行试验，以检验现场视频监控运动(有氧+ 阻力)干预将改善心脏和体能；肌肉质量、力量和功能； 和内皮功能。坚持是现场提供儿科运动干预的一个主要限制， 由于距离现场较远、交通不便、缺课或 工作日。为了克服这些挑战，我们将利用实时视频会议来交付受监督的 健身房。在我们的试点运动干预中，这种方法导致了极好的依从性(&gt；85%) 并改善运动能力和内皮功能。这项提案旨在确定 干预改善：(目标1)心脏和体力(主要结果：最大摄氧量)、(目标2)肌肉质量 力量和功能；以及(目标3)儿童Fontan患者的内皮功能。我们的多学科团队 专家将评估现场视频监督的锻炼干预的有效性，该干预措施严格设计为 最大限度地遵守和改善与以下疾病相关的儿童Fontan患者的关键和新的健康措施 长期结果不佳。运动作为非药物治疗方式在儿童Fontan中的应用 患者代表着一种范式的转变，标准疗法已经失败。我们的最终目标是翻译 将这一模式作为早期干预儿童Fontan患者的运动处方应用于临床 并降低长期发病率和死亡率，与NIH开发循证证据的使命保持一致 改善患有慢性病的青年的结果的新方法的数据。

PROJECT SUMMARY Survival of children with single ventricles (“half a heart”) beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By the age of 40, 50% of Fontan patients will have died or undergone heart transplantation. With >1,000 Fontan palliations performed in the US annually, there is a burgeoning population of Fontan patients at risk for progressive heart failure and death. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity, associated with a greater risk of morbidity and mortality, in addition to decreased muscle mass, abnormal muscle function, and endothelial dysfunction contributing to disease progression. In adult patients with two ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Furthermore, none of these interventions have studied the impact of exercise on muscle mass or mitochondrial function, or endothelial function. We propose a milestone-driven, randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic + resistance) intervention will improve cardiac and physical capacity; muscle mass, strength and function; and endothelial function. Adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or work days. To overcome these challenges, we will utilize live-video conferencing to deliver the supervised exercise sessions. In our pilot exercise interventions, this approach resulted in excellent adherence (>85%) and improved exercise capacity and endothelial function. This proposal is designed to determine if the intervention improves: (Aim 1) cardiac and physical capacity (primary outcome: VO2 max), (Aim 2) muscle mass strength and function; and (Aim 3) endothelial function in pediatric Fontan patients. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. The use of exercise as a non-pharmacologic treatment modality in pediatric Fontan patients represents a paradigm shift, where standard therapies have failed. Our ultimate goal is the translation of this model to clinical application as an ”exercise prescription” to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality, in alignment with the NIH’s mission to develop evidence-based data for new approaches to improve outcomes in youth with chronic conditions.