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.

项目摘要 /摘要 候选人最近加入了马萨诸塞州综合医院（MGH）的工作人员 绩效计划（CPP），一个独特的团体，其目标包括进行顶级人类健康和 绩效研究。 CPP的核心任务是使用纵向研究设计来检查心脏 适应运动。该建议将该模型扩展到一个新的方向以评估心脏代谢 通过与Brigham和妇女医院的研究合作，使用正电子发射断层扫描（PET）。 该提案的重点是在许多心脏病中发展的左心室肥大（LVH）， 包括肥厚的心肌病（HCM），具有独立的负预后意义。在 与病理LVH相反，运动诱导的LVH（EI-LVH）通常被认为是适应性的。区分 LVH是由于运动还是HCM是临床挑战，因为HCM是最重要的 年轻运动员突然死亡的原因。尽管心肌代谢似乎以 病理LVH，与心力衰竭的发展有关，对心肌的了解很少 Ei-LVH中的代谢。该研究建议的两个主要目标是定义心肌代谢是否 分析将能够确定将EI-LVH与HCM区分开，并通过此进一步获取 关于运动能力和心肌功能如何在这两种形式的情况下差异很大的机械洞察力 LVH。具体而言，我们假设心肌代谢效率（MME），底物的表征 利用，微血管功能和循环推论血浆microRNA（miRNA）将提供 科学新颖和临床上具有优越的技术，可将适应性与病理LVH分离。 为了实现这些目标，申请人提出了一项纵向，重复的措施研究，其中运动员 将使用心脏宠物，超声心动图和运动前后的miRNA分析进行检查 - 具体的运动训练。心脏宠物评估将包括对心肌氧化的测量 在休息和急性运动挑衅时，代谢，代谢效率和底物利用率。 LVH训练有素的运动员的心肌代谢谱将与轻度患者进行比较 HCM和健康对照组，在没有运动训练干预的情况下，将同样研究。 候选人的职业发展计划包括运动生理学的高级培训，心脏 成像和研究方法，都是在独特的多学科团队的指导下。科学 在这笔赠款中提出的将为旨在操纵心肌代谢的未来研究奠定基础 在自适应生理学和心血管疾病的各个方面，这将构成 候选人的未来R01提案。在K23奖的过程中，候选人的目标是发展成一个 独立的临床心血管研究者。