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

先天性心脏病心力衰竭：心肌纤维化的作用

• 批准号: 7921682
• 负责人: Craig Stanford Broberg
• 金额: $ 13.17万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921682
• 关键词: Address; Adult; Aldosterone; Architecture; Brain natriuretic peptide; Cardiac; Cardiology; Cardiovascular Physiology; Cardiovascular system; Clinical Research; Collagen; Collagen Type I; Collagen Type III; Commit; Data; Development; Development Plans; Diagnostic; Diffuse; EFRAC; Eisenmenger Complex; Ensure; Exercise; Fibrosis; Functional disorder; Funding; Gelatinase A; Goals; Health Sciences; Heart Diseases; Heart failure; Hyperaldosteronism; Lisinopril; Magnetic Resonance Imaging; Matrix Metalloproteinase Inhibitor; Mediating; Mentors; Methods; Myocardial; Oregon; Pathway interactions; Patients; Peptides; Plasma; Prevalence; Publications; Randomized; Research; Research Personnel; Resources; Role; Scientist; Serum; Spironolactone; Subgroup; Tetralogy of Fallot; Time; Tissue Inhibitor of Metalloproteinase-1; Tissues; Training; Universities; Walking; congenital heart disorder; design; in vivo; indexing; interest; medical specialties; novel; programs; therapeutic target

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.

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独立的临床医生-科学家。Broberg博士获得了成人先天性心脏病（ACHD）和心脏MRI的亚专业培训。他在ACHD临床研究的设计、执行和出版方面取得了成功，并寻求进一步开展这项研究所需的资源。俄勒冈州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成功独立研究的长期目标。因此，本申请包括一个拟议的发展计划，由心脏病科完全支持，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，先进的超声心动图培训，与其他实验室有重叠的利益，并成功申请独立的研究资金。该研究计划提出了ACHD中的心力衰竭，这是几个特定诊断亚组中的常见最终途径。虽然发病率不断上升，但目前对ACHD相关性心力衰竭的研究很少。有限的数据支持醛固酮介导的纤维化存在的假设，因此是一个潜在的治疗靶点。使用新的MRI方法定量体内弥漫性心肌纤维化，我们的目标是：1）证明纤维化及其与特定ACHD亚组心血管功能障碍的相关性，2）将纤维化与醛固酮和胶原合成的变化联系起来，然后3）通过定量使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联系起来来证明其作用。