Profiles of Myocardial Metabolism in "Gray-Zone" Athletic Left Ventricular Hypertrophy versus Hypertrophic Cardiomyopathy

“灰色地带”运动性左心室肥厚与肥厚性心肌病的心肌代谢概况

• 批准号: 10318121
• 负责人: MEAGAN M WASFY
• 金额: $ 20.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-25 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318121
• 关键词: Acetates; Activities of Daily Living; Acute; Address; Affect; Age; Athletic; Biology; Blood Pressure; Caliber; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cell Respiration; Clinical; Collaborations; Coronary; Coupling; Dangerousness; Data; Development; Development Plans; Diagnosis; Echocardiography; Educational Intervention; Evaluation; Exercise; Exercise Physiology; Future; Gender; General Hospitals; Genetic; Glucose; Goals; Grant; Health; Heart; Heart Diseases; Heart Rate; Heart failure; Hospitals; Human; Hypertrophic Cardiomyopathy; Impairment; Laboratories; Left Ventricular Hypertrophy; Left Ventricular Mass; Link; Longitudinal Studies; Massachusetts; Measurement; Measures; Mechanics; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Metabolism; MicroRNAs; Mission; Modeling; Molecular; Morphology; Muscle; Myocardial; Nonesterified Fatty Acids; Oxygen Consumption; Palmitates; Pathologic; Patients; Pattern; Performance; Phenotype; Physiology; Plasma; Positioning Attribute; Positron-Emission Tomography; Process; Property; Pump; Research; Research Design; Research Methodology; Research Personnel; Research Proposals; Rest; Risk; Science; Scientist; Sports; Strenuous Exercise; Stroke Volume; Sudden Death; Syndrome; Techniques; Testing; Tracer; Training; Translating; Uncertainty; Woman; Work; base; cardiogenesis; career; career development; circulating microRNA; comparative; design; exercise capacity; exercise program; exercise training; heart imaging; heart metabolism; hemodynamics; indexing; insight; metabolic profile; multidisciplinary; novel; nuclear imaging; paracrine; preservation; pressure; primary outcome; prognostic; programs; response; sedentary; stressor; sudden cardiac death; tool; translational study

PROJECT SUMMARY / ABSTRACT The candidate recently joined the staff at Massachusetts General Hospital (MGH) in the Cardiovascular Performance Program (CPP), a unique group whose goals include conducting top-caliber human health and performance research. A core mission of the CPP is to use longitudinal study design to examine cardiac adaptations to exercise. This proposal expands this model in a novel direction to evaluate cardiac metabolism using positron emission tomography (PET) through research collaboration with Brigham and Women's Hospital. This proposal focuses on left ventricular hypertrophy (LVH), which develops in numerous cardiac diseases, including hypertrophic cardiomyopathy (HCM), and has independent negative prognostic implications. In contrast to pathologic LVH, exercise-induced LVH (EI-LVH) is generally considered adaptive. Differentiating whether LVH is due to exercise or HCM is a clinical challenge with critical implications because HCM is the top cause of sudden death in young athletes. Though myocardial metabolism appears to be impaired in forms of pathologic LVH and is linked to the development of heart failure, comparatively little is known about myocardial metabolism in EI- LVH. The two major goals of this research proposal are to define if myocardial metabolic profiling will be capable of definitively differentiating EI-LVH from HCM AND, through this, to gain further mechanistic insight into how exercise capacity and myocardial function differ so widely in these two forms of LVH. Specifically, we hypothesize that characterization of myocardial metabolic efficiency (MME), substrate utilization, microvascular function, and circulating corollary plasma microRNAs (miRNA) will provide scientifically novel and clinically superior techniques for separating adaptive from pathologic LVH. To achieve these goals, the applicant proposes a longitudinal, repeated measures study in which athletes will be examined using cardiac PET, echocardiography, and circulating miRNA profiling before and after sport- specific exercise training. Cardiac PET assessment will include measurement of myocardial oxidative metabolism, metabolic efficiency, and substrate utilization, both at rest and with acute exercise provocation. The myocardial metabolic profiles of trained athletes with LVH will be compared to that of patients with mild HCM and healthy controls, who will be similarly studied in the absence of an exercise training intervention. The candidate's career development plan includes advanced training in exercise physiology, cardiac imaging, and research methodology, all under the mentorship of a unique multidisciplinary team. The science proposed in this grant will set the stage for future studies designed to manipulate myocardial metabolism across the spectrums of adaptive physiology and cardiovascular disease, which will form the basis of the candidate's future R01 proposals. Over the course of the K23 award, the candidate's goal is to develop into an independent clinical cardiovascular investigator.

项目概要/摘要 该候选人最近加入了马萨诸塞州总医院 (MGH) 心血管科的工作人员。 绩效计划 (CPP)，一个独特的团体，其目标包括开展顶级人类健康和 性能研究。 CPP 的核心任务是使用纵向研究设计来检查心脏 对运动的适应。该提案将该模型扩展到评估心脏代谢的新方向 通过与布莱根妇女医院的研究合作，使用正电子发射断层扫描 (PET)。 该提案的重点是左心室肥大（LVH），它在多种心脏病中发生， 包括肥厚型心肌病（HCM），并具有独立的负面预后影响。在 与病理性 LVH 相比，运动诱发的 LVH (EI-LVH) 通常被认为是适应性的。差异化 左心室肥厚 (LVH) 是由运动引起还是由肥厚性心肌病 (HCM) 引起，这是一项具有重大影响的临床挑战，因为肥厚性心肌病 (HCM) 是最重要的原因 年轻运动员猝死的原因。尽管心肌代谢似乎以以下形式受损 病理性 LVH 并与心力衰竭的发展有关，但人们对心肌知之甚少 EI-LVH 中的代谢。该研究计划的两个主要目标是确定心肌代谢是否 分析将能够明确区分 EI-LVH 和 HCM，并通过此获得进一步的信息 从机制上洞察运动能力和心肌功能在这两种形式中的差异如此之大 左心室肥厚。具体来说，我们假设心肌代谢效率（MME）、底物的表征 利用率、微血管功能和循环血浆 microRNA (miRNA) 将提供 用于区分适应性和病理性 LVH 的科学新颖且临床优越的技术。 为了实现这些目标，申请人提出了一项纵向、重复测量研究，其中运动员 将在运动前后使用心脏 PET、超声心动图和循环 miRNA 分析进行检查 具体的运动训练。心脏 PET 评估将包括心肌氧化的测量 休息时和急性运动刺激下的新陈代谢、代谢效率和底物利用率。 训练有素的患有 LVH 的运动员的心肌代谢特征将与患有轻度 LVH 的患者进行比较 HCM 和健康对照，将在没有运动训练干预的情况下进行类似的研究。 候选人的职业发展计划包括运动生理学、心脏病学等方面的高级培训 成像和研究方法，所有这些都在一个独特的多学科团队的指导下进行。科学 这笔赠款中提出的建议将为未来旨在操纵心肌代谢的研究奠定基础 跨越适应性生理学和心血管疾病的各个领域，这将构成 候选人未来的 R01 提案。在 K23 奖项的学习过程中，候选人的目标是发展成为 独立临床心血管研究者。