Exercise Training in Heart Failure: structural and functional cardiac remodeling

描述（由申请人提供）： 收缩性心力衰竭（HF）的患病率在不断增长的老年人群中很高1 -3。进行性心脏重塑和心输出量恶化是HF相关运动不耐受和生活质量的关键因素1。即使在实施适度重塑的医疗和器械治疗后，运动耐量仍然受损。虽然运动训练已被证明可以提高运动能力，但促进这种益处的机制仍不清楚。骨骼肌和血管系统的外周适应性至少提供了一些益处，但是逆转心脏重塑（超出药物和器械治疗的影响）可能是额外的4 -6。我们建议研究2种不同类型的运动对心脏形态以及收缩和舒张性能和相关功能增益的影响。我们将比较传统的有氧训练和一种新的吸气肌训练方案。IMT是一种特殊类型的运动训练，可能对不太可能耐受有氧训练的虚弱、虚弱的HF患者特别有用。以前没有研究过IMT对重塑的影响。 拟议的超声心动图初步研究建立在一项受资助的VA Merit F0834-R“运动疗法减少心力衰竭症状;获益排序机制”（PI，Forman）的基础上，该研究比较了老年（年龄50岁）收缩期（EFd 40%）HF患者的不同运动训练模式。最初的研究评估了受运动训练影响的外周机制，但并非旨在评估心脏重塑。拟议的试点研究提供了一个重要的补充分析，即，它增加了心脏重塑的评估以及收缩和舒张性能的相关变化。将研究年龄≥ 50岁的男性和女性（N=75）收缩期HF患者（LVEF d40%）。患者将被随机分配至三组之一（IMT [n=30]或有氧[n=30]或对照[n=15]）。在为期12周、每周3次的有氧训练方案、IMT方案和常规护理方案之前和之后，将进行一系列全面的功能评估以及超声心动图检查。 具体目的：（1）采用常规方法，分析运动训练对左心室结构和功能的影响， 收缩和舒张功能的新指标。我们假设，与对照组相比，运动训练将减少左心室舒张末期和收缩末期容积，增加射血分数（EF）以及局部应变。(b)运动训练可增加二尖瓣环舒张早期血流速度（e '），并降低二尖瓣早期血流速度（E）与e'的比值（E/e '）。(c)IMT在抗重塑获益方面不劣于有氧训练，两种形式的训练均上级对照组。（二）、探索改善心脏重塑和生理学对功能和定性终点的获益。我们假设（a）运动训练相关的心脏改善将导致有氧功能参数（峰值VO 2和VE/VCO 2斜率）的改善。(b)运动训练相关的心脏改善将导致有氧功能参数的改善和生活质量的改善（通过问卷测量）。

DESCRIPTION (provided by applicant): Prevalence of systolic heart failure (HF) is high among the growing population of older adults1-3. Progressive cardiac remodeling and deteriorating cardiac output have been implicated as key factors underlying HF-related exercise intolerance and quality of life1. Even after implementing medical and device therapies that moderate remodeling, exercise tolerance remains impaired. While exercise training has been demonstrated to improve exercise capacity, mechanisms facilitating this benefit remain unclear. Peripheral adaptations in the skeletal muscle and vasculature provide at least some benefit, however reverse cardiac remodeling (beyond effects of pharmacological and device therapies) may be additive4-6. We propose to study the impact of 2 different types of exercise on cardiac morphology as well as systolic and diastolic performance and related functional gains. We will compare traditional aerobic training to a novel regimen of inspiratory muscle training (IMT). IMT is a specific type of exercise training that may be particularly useful for frail, infirmed HF patients who are unlikely to tolerate aerobic trainin. Effects of IMT on remodeling have not been previously studied. The proposed echocardiography pilot study builds on a funded VA Merit F0834-R "Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit" (PI, Forman) that compares different modes of exercise training in older (agee50yrs) systolic (EFd40%) HF patients. The original study assesses peripheral mechanisms affected by exercise training, but was not designed to assess cardiac remodeling. The proposed pilot study provides a vital complementary analysis, i.e., it adds assessments of cardiac remodeling as well as related changes in systolic and diastolic performance. Male and female (N=75) systolic HF patients (LVEF d40%) aged e50 years will be studied. Patients will be randomized into one of three groups (IMT [n=30] or aerobic [n=30] or control [n=15]). A comprehensive battery of functional assessments as well as echocardiographic examination will be performed before and after a 12-week, 3x/weekly regimen of aerobic training vs. IMT vs. usual care. Specific Aims are (1) to analyze exercise training effects on left ventricular structure and function using conventional and novel indices of systolic and diastolic function. We hypothesize that exercise training will decrease left ventricular end-diastolic and end-systolic volumes and increase ejection fraction (EF) as well as regional strain compared to controls. (b) exercise training will increase mitral annular early diastolic velocity (e') as well as decrease the ratio (E/e') of early mitral inflow velocity (E) and e'. (c) IMT will be non-inferior to aerobic training in relation to anti-remodelin benefit and both forms of training will be superior compared to controls. (2). To explore the benefits of improved cardiac remodeling and physiology on functional and qualitative endpoints. We hypothesize (a) that exercise training-related cardiac improvements will lead to improved aerobic functional parameters (peak VO2 and VE/VCO2 slope). (b) that exercise training-related cardiac improvements will lead to improved aerobic functional parameters and improved quality of life (as measured by questionnaires).