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

项目摘要 新生儿期后单心室（“半个心脏”）儿童的生存率大幅提高 方丹姑息手术的效果然而，长期发病率仍然很高。到40岁时，50%的Fontan患者 已经死亡或接受心脏移植。美国每年进行超过1,000例Fontan姑息治疗， 有进行性心力衰竭和死亡风险的Fontan患者群体迅速增加。的因素 导致Fontan患者心力衰竭发作和进展的因素仍不完全清楚。然而，在这方面， 已经确定Fontan患者运动能力差，与更大的发病风险相关， 死亡率，以及肌肉质量下降、肌肉功能异常和内皮功能障碍 促进疾病进展。在患有两个心室和心力衰竭的成年患者中， 能力、肌肉质量和肌肉力量是不良结果的有力预测因素， 干预措施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经证明运动是安全的 有效;然而，这些研究是在小的，异质的群体中进行的，大多数人很少 丰唐病人。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。我们提出了一个里程碑驱动的，随机对照的 在儿童Fontan患者中进行的一项试验，旨在检验现场视频监督运动（有氧+ 阻力）干预将改善心脏和身体的能力;肌肉质量，力量和功能; 和内皮功能。依从性是现场提供的儿科运动干预的主要限制， 由于远离现场、交通困难和缺课，依从率低至10%， 工作日。为了克服这些挑战，我们将利用实时视频会议来提供监督 练习会话。在我们的试点运动干预中，这种方法导致了极好的依从性（>85%） 并改善运动能力和内皮功能。本提案旨在确定 干预改善：（目标1）心脏和体能（主要结局：最大摄氧量），（目标2）肌肉质量 强度和功能;（目的3）儿童Fontan患者的内皮功能。我们的多学科团队 专家们将评估现场视频监督运动干预的有效性， 最大限度地提高依从性，并改善儿童Fontan患者的关键和新的健康指标， 长期效果不佳。运动作为非药物治疗方式在儿童Fontan中的应用 患者代表了一种范式转变，标准疗法已经失败。我们的最终目标是翻译 该模型的临床应用作为“运动处方”，以早期干预儿童Fontan患者 并降低长期发病率和死亡率，符合NIH的使命， 为改善慢性病青年治疗结果的新方法提供数据。

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.