Heart Failure in Congenital Heart Disease: The role of Myocardial Fibrosis

描述(由申请人提供)：本提案旨在确保克雷格·布罗伯格博士继续发展成为一名独立的临床医生-科学家。Broberg博士接受过成人先天性心脏病(ACHD)和心脏核磁共振的专科培训。他成功地设计、执行和发表了ACHD的临床研究，并寻求必要的资源来进一步开展这项研究。俄勒冈健康与科学大学的研究架构完全支持并投资于促进他在ACHD方面成功独立研究的长期目标。因此，这项申请包括一项由心脏病学部全力支持的拟议发展计划，包括受保护的研究时间、承诺的指导、完成临床研究硕士学位、高级超声心动图培训、参与其他兴趣重叠的实验室，以及成功申请独立研究资金。提出的研究计划针对ACHD的心力衰竭，这是几个特定诊断亚组中常见的最终途径。虽然发病率有所上升，但目前对ACHD相关性心力衰竭的研究很少。现有的有限数据支持这一假设，即醛固酮介导的纤维化是存在的，因此是一个潜在的治疗靶点。我们使用新的MRI方法对体内弥漫性心肌纤维化进行量化，目的是：1)在特定的ACHD亚组中显示纤维化及其与心血管功能障碍的关系；2)将纤维化与醛固酮和胶原合成的变化联系起来；3)通过量化服用螺内酯一年后纤维化的间隔变化并将其与胶原合成和结构变化相关联来证明其作用。

DESCRIPTION (provided by applicant): This proposal seeks to ensure the continued development of Dr. Craig Broberg towards becoming an independent Clinician-Scientist. Dr. Broberg has obtained sub-specialty training in adult congenital heart disease (ACHD), and cardiac MRI. He has been successful in the design, execution, and publication of clinical studies in ACHD, and seeks the resources necessary to cany this study further. The research architecture at Oregon Health and Science University is fully supportive and invested in facilitating his longterm goal of successful independent research in ACHD. Therefore, this application includes a proposed development plan, fully supported by the Division of Cardiology, consisting of protected research time, committed mentoring, completion of a Masters in Clinical Research degree, advanced echocardiographic training, participation with other labs with overlapping interests, and successful application for independent research funding. The Research Plan proposed addresses heart failure in ACHD, a common final pathway in several specific diagnostic subgroups. Though increasing in prevalence, there is little research in ACHDrelated heart failure at present. The limited data available support the hypothesis that aldosterone-mediated fibrosis is present and thus a potential therapeutic target. Using novel MRI methods to quantify diffuse myocardial fibrosis in-vivo, we aim to: 1) demonstrate fibrosis and its association with cardiovascular dysfunction in specific ACHD subgroups, 2) relate fibrosis to aldosterone and changes in collagen synthesis, and then 3) prove its role by quantifying the interval change in fibrosis after a year of spironolactone and correlating this with collagen synthesis and structural change.