Exercise Training in Heart Failure: structural and functional cardiac remodeling

收缩期心力衰竭（HF）的患病率在不断增长的老年人中很高1-3。

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 training. 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-remodeling 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).