Mentoring patient-oriented research in deep phenotyping of cardiac function for heart failure prevention

阿米尔·沙阿博士是哈佛医学院医学副教授，也是一位活跃的临床医生。 布里格姆妇女医院(BWH)的心脏病专家和心血管成像师。他的整个职业目标是 为诊断、治疗和预防心力衰竭(HF)和心力衰竭做出实质性贡献 特别是保留射血分数(HFpEF)-通过有影响力的研究和有效的指导 下一代调查人员。他开发了一项成功的、独立的以患者为导向的研究(POR) 旨在通过将心脏成像整合到 基于医院的前瞻性生理学研究、多中心流行病学队列和随机临床研究 审判。他领导了影响深远的出版物，告知HFpEF病理生理学、诊断和管理，以及 已经获得了持续的NIH资金(PI在2个有效的R01赠款上)。他是22名学员的主要导师 到目前为止，他的计划提供了一个独特的POR培训平台，通过与 哈佛大学CTSA、BWH心血管成像T32计划和临床学位授予计划 哈佛医学院和公共卫生学院的调查。他对这项K24提案的目标是 (一)透过教学和同辈主导的工作坊，提高导师的质素和范围；。(二) 扩大他的研究计划，使之包括“经济”科学；以及(3)发展分析高密度脂蛋白的专门知识。 与成像表型和临床结果相关的维度“组学”数据。受K24保护的时间 将使沙阿博士能够在指导方面进行说教式和同行主导的培训，扩大他的指导活动， 并从事“经济学”科学方面的课程作业和“实践”培训。来自K24的资金将支持 他的研究计划扩展到翻译蛋白质组学和基因组学，包括计算 生物支持。HFpEF是常见的、病态的，并且患病率在增加，但没有有效的疾病特异性。 目前已有治疗方法。虽然导致HFpEF的左心功能障碍是一个激烈的调查重点，但几乎没有 已知的促进心脏功能保存的生物学途径 共病(心脏复原力)。这是一个严重错失的机会，无法制定促进 心功能正常，预防心力衰竭。这项提案的具体科学目标是定义循环 个体蛋白质和蛋白质网络：(1)与运动有正相关，也有负相关- HFpEF特有的血流动力学紊乱；(2)与晚年心脏弹性有关；以及(3) 根据使用基因组数据的研究，最有可能是心脏弹性的中介。目标1将在 预期在BWH接受侵入性运动测试的患者。目标2和目标3将在#年执行 社区人群中的动脉粥样硬化风险，在杰克逊心脏研究中重复。合成 这些与沙阿现有研究计划相结合的经济学方法将使沙阿博士在垂直领域独树一帜 增进对HFpEF病理生物学的了解，同时丰富他的学员在POR方面的培训机会。

Dr Amil Shah is an Associate Professor of Medicine at Harvard Medical School and an active clinical cardiologist and cardiovascular imager at Brigham and Women's Hospital (BWH). His overall career goal is to make substantial contributions to the diagnosis, treatment, and prevention of heart failure (HF) – and HF with preserved ejection fraction (HFpEF) in particular – through impactful research and effective mentoring of the next generation of investigators. He has developed a successful, independent patient oriented research (POR) program aiming to define the cardiac perturbations responsible for HFpEF by integrating cardiac imaging into prospective hospital-based physiologic studies, multicenter epidemiologic cohorts, and randomized clinical trials. He has led impactful publications informing HFpEF pathophysiology, diagnosis, and management, and has secured continuous NIH funding (PI on 2 active R01 grants). He has been primary mentor to 22 trainees to-date, and his program provides a unique platform for training in POR which is amplified by integration with the Harvard CTSA, BWH cardiovascular imaging T32 program, and degree-granting programs in clinical investigation at Harvard Medical School and School of Public Health. His objectives for this K24 proposal are (1) to improve the quality and scope of his mentoring by engaging in didactic and peer-led workshops; (2) to expand his research program to include `-omic' science; and (3) to develop expertise in analysis of high- dimensional `-omic' data to relate to imaging phenotypes and clinical outcomes. Protected time from the K24 will enable Dr Shah to pursue didactic and peer-led training in mentoring, to expand his mentoring activities, and to engage in coursework and `hands-on' training in `-omic' science. Funds from the K24 will support expansion of his research program into translational proteomics and genomics, including computational biology support. HFpEF is common, morbid, and increasing in prevalence, but no efficacious disease-specific therapy currently exists. While LV dysfunction underlying HFpEF is an intense focus of investigation, little is known regarding biological pathways promoting the preservation of cardiac function in the face of detrimental co-morbidities (cardiac resilience). This is a critical missed opportunity to develop interventions promoting normal cardiac function to prevent HF. The specific scientific aims of this proposal are to define circulating individual proteins and protein networks that (1) positively and negatively correlate with exercise- hemodynamic perturbations characteristic of HFpEF; (2) associate with cardiac resilience in late life; and (3) are most likely to be mediators of cardiac resilience based on studies using genomic data. Aim 1 will occur in patients prospectively enrolled at BWH to undergo invasive exercise testing. Aims 2 and 3 will be performed in the Atherosclerosis Risk in Communities cohort, with replication in the Jackson Heart Study. Synthesizing these `-omic' approaches with his existing research program will uniquely position Dr Shah to vertically advance understanding of HFpEF pathobiology, while enriching training opportunities in POR for his mentees.