Exercise-Induced Concentric Left Ventricular Hypertrophy: Unrecognized Pathology

 描述（由申请人提供）：当心血管系统暴露于剧烈运动的固有血流动力学应激源时，运动诱导的左心室肥大（LVH）（“适应性LVH”的经典范例）发生。同心运动诱导的LVH（CEI-LVH）是响应于基于重复力量的运动训练而发展的几何LVH亚型，其在历史上被认为是完全良性的过程。然而，来自PI小组的最近积累的数据表明，CEI-LVH的最初适应性过程最终进展为病理性和不完全可逆的表型，其特征在于明显的舒张功能障碍和处理血流动力学应激的能力受损。此外，为准备当前提案而收集的初步数据表明，与CEI-LVH相关的功能异常在运动戒断后似乎不完全可逆。因此，CEI-LVH似乎是一种获得性的、目前未被认识到的、并且完全可预防的早期生命病理形式，其可作为高血压心脏病和射血分数保留的心力衰竭综合征的先兆，这两种综合征都是主要的公共卫生危机。使用一个已建立的平台，在人类CEI-LVH的研究，目前的建议，旨在应用多模态成像，生化分析，和生理激发，探索功能的影响，机制的基础，和可逆性CEI-LVH。进行本研究的研究团队在使用纵向重复测量研究设计方面具有丰富的经验，并已证明能够成功招募和研究心肌重塑发展和消退期间的个体。该提案的一个关键特征是，它利用了哈佛运动员计划的现有基础设施，该计划旨在研究体育锻炼对心血管的反应，从而利用了既定的受试者招募过程和疾病量化协议。这项研究的结果有望促进我们对LVH过程的机制理解，并开始阐明运动性LVH的临床意义。

 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.