Exercise-Induced Concentric Left Ventricular Hypertrophy: Unrecognized Pathology

运动引起的向心性左心室肥大：尚未认识到的病理学

• 批准号: 9099892
• 负责人: Aaron Baggish
• 金额: $ 33.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099892
• 关键词: Abstinence; Acute; Address; Affect; Age; American; Architecture; Area; Benign; Biochemical; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Size; Chronic; Clinical; Control Groups; Data; Development; Diffuse; Disease; EFRAC; Enrollment; Equilibrium; Excision; Exercise; Fibrosis; Functional disorder; Gender; Geometry; Health; Heart failure; Height; Human; Hypertrophy; Image; Imaging Techniques; Impairment; Individual; Isometric Exercise; Isotonic Exercise; Lead; Left; Left Ventricular Dysfunction; Left Ventricular Hypertrophy; Left Ventricular Mass; Life; Longitudinal Studies; Magnetism; Measures; Mediator of activation protein; Methodology; Morbidity - disease rate; Muscle Cells; Myocardial; Participant; Pathologic; Pathology; Phenotype; Physical Exercise; Physiological; Physiology; Preparation; Process; Protocols documentation; Public Health; RNA; Recruitment Activity; Research Design; Research Infrastructure; Rest; Risk; Sports; Stimulus; Strenuous Exercise; Stress; Syndrome; Testing; Tissues; Uncertainty; Ventricular; Ventricular Remodeling; Weight; Work; base; clinically relevant; cohort; coronary fibrosis; design; exercise training; experience; extracellular; hemodynamics; hypertensive heart disease; imaging modality; mortality; pressure; prognostic; programs; prospective; response; sedentary; strength training; stressor

 DESCRIPTION (provided by applicant): Exercise-induced left ventricular hypertrophy (LVH), the classic paradigm of "adaptive LVH", develops when the cardiovascular system is exposed to the inherent hemodynamic stressors of vigorous exercise. Concentric exercise-induced LVH (CEI-LVH), the geometric LVH sub-type that develops in response to repetitive strength- based exercise training, has historically been regarded as a completely benign process. However, recently accrued data from the PI's group suggest that the initially adaptive process of CEI-LVH ultimately progresses into a pathologic and incompletely reversible phenotype characterized by overt diastolic dysfunction and an impaired ability to handle hemodynamic stress. Further, preliminary data collected in preparation for the current proposal suggest that functional abnormalities associated with CEI-LVH appear to be incompletely reversible following exercise abstinence. Thus, CEI-LVH appears to be an acquired, currently unrecognized, and fully preventable early life form of pathology that may serve as a pre-cursor to the syndromes of hypertensive heart disease and heart failure with preserved ejection fraction, both major public health crises. Using an established platform for the study of CEI-LVH in humans, the current proposal seeks to apply multi-modality imaging, biochemical profiling, and physiologic provocation to explore the functional implications, mechanistic underpinnings, and reversibility of CEI-LVH. The investigative team assembled to conduct this study has extensive experience using longitudinal, repeated measures study designs and has demonstrated the ability to successfully recruit and study individuals during the development and regression of myocardial remodeling. A critical feature of this proposal is that it leverages the existing infrastructure ofthe Harvard Athlete Initiative, an program design to study the cardiovascular response to physical exercise, thereby capitalizing on established subject recruitment processes and disease quantification protocols. Results from the proposed study are expected to advance our mechanistic understanding of the LVH process and to begin to clarify the clinical implications exercise-induced LVH.

 描述(申请人提供)：运动性左心室肥厚(LVH)是“适应性左心室肥厚”的经典范例，当心血管系统暴露于剧烈运动固有的血流动力学应激源时发生。向心性运动诱导的左心室肥厚(CEI-LVH)是根据重复力量运动训练而发展起来的几何左心室肥厚亚型，历史上一直被认为是一个完全良性的过程。然而，PI小组最近积累的数据表明，CEI-LVH最初的适应过程最终发展为一种病理的、不完全可逆的表型，其特征是明显的舒张期功能障碍和处理血流动力学应激的能力受损。此外，在准备本提案时收集的初步数据表明，运动戒断后与CEI-LVH相关的功能异常似乎是不完全可逆的。因此，CEI-LVH似乎是一种获得性的、目前未被认识到的、完全可预防的早期生命病理形式，可能是高血压心脏病和射血分数保留的心力衰竭综合征的前驱指标，这两种疾病都是重大的公共卫生危机。利用已建立的人类CEI-LVH研究平台，目前的提议试图应用多模式成像、生化图谱和生理激发来探索CEI-LVH的功能含义、机制基础和可逆性。为进行这项研究而组建的研究团队拥有使用纵向、重复测量研究设计的丰富经验，并证明了在心肌重塑的发展和消退过程中成功招募和研究个体的能力。这项建议的一个关键特点是，它利用了哈佛运动员倡议的现有基础设施，该计划旨在研究体育锻炼对心血管的反应，从而利用既定的受试者招募程序和疾病量化方案。这项拟议研究的结果有望促进我们对左心室肥厚过程的机制理解，并开始阐明运动性左心室肥厚的临床意义。