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.
Strength-based exercise training (isometric physiology) leads to the development of concentric left ventricular hypertrophy CEI-LVH). Recent work demonstrates that chronic CEI-LVH is associated with impaired left ventricular diastolic dysfunction, a well-documented cause of significant morbidity and mortality. Using a unique longitudinal study design, this proposal aims to develop a comprehensive profile of chronic CEI-LVH by delineating the magnitude of associated left ventricular dysfunction, the underlying biochemical mediators and tissue architecture, and the reversibility following prescribed exercise abstinence. The work will address critical areas of scientific uncertainty with important attendant public health implications.
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