VENTRICULAR REMODELING IN HEART FAILURE

申请人在以患者为中心的研究和临床研究人员培训方面取得了成功的记录。然而，由于广泛而苛刻的临床任务，他只有10%的时间受到以患者为中心的临床研究的保护。如果获奖，这笔赠款将允许申请者将50%的时间用于执行受资助的CHF临床研究和启动新项目。更重要的是，这一奖项将使申请者能够更狭隘地将其资助的面向患者的研究计划集中在充血性心力衰竭(CHF)的左心室(LV)重塑领域，并获得将分子生物学的新发展转化为临床研究所需的新技能。目前，申请者是由NHLBI/VA合作研究计划赞助的BEST(Beta-Blocker评估生存试验)研究的联合首席研究员和超声心动图核心实验室主任。这项最佳超声心动图子研究的具体目的是：1)确定哪些超声心动图变量是CHF患者存活和血流动力学改善的独立预测因素；2)评估β-受体阻滞剂治疗是否改善了左室重构；3)评估收缩储备是否预示着左室重构对β-受体阻滞剂治疗的有利反应。这项奖励，如果授予，将允许在两年内完成这一项目。此外，研究人员正在开发一种新的方法，通过使用新的全氟碳填充微球的声学造影来定量评估心肌血流储备比。这种方法已经在狗身上得到了验证，它在人类身上的验证最近也得到了资助。研究人员的长期目标是：1)评估微血管功能在临床心力衰竭和左心室重构发展中的作用；2)评估特定的心力衰竭疗法对微血管功能的影响。这项工作计划在初步验证研究完成后，在这项赠款提案的后几年进行。最后，如果获得这项资助，研究人员将可以进行涉及慢性二尖瓣反流中左室重构分子信号的转译研究。该项目的长期目标是识别那些即将发生左室衰竭的患者，以便进行早期手术干预，并为慢性二尖瓣反流和扩张型心肌病的偏心性左室重构开发治疗靶点。

The applicant has established a record of success in patient- oriented research and training of clinical investigators. However, only 10 percent of his time is protected for patient-oriented clinical research because of extensive and demanding clinical duties. If awarded, this grant will allow the applicant to devote 50 percent of his time performing funded clinical CHF studies and initiated novel projects. More importantly, this award will enable the applicant to more narrowly focus his funded patient-oriented research program in the area of left ventricular (LV) remodeling in congestive heart failure (CHF) and to acquire new skills need to translate new developments in molecular biology into clinical research. Currently, the applicant is co-principal investigator and Director of the Echocardiography Core Lab for the BEST (Beta-Blocker Evaluation of Survival Trial) Study sponsored by the NHLBI/VA Cooperative Studies Program. The specific aims of this BEST Echocardiography Substudy are to 1) determine which echocardiographic variables are independent predictors of survival and hemodynamic improvement in CHF, 2) assess whether beta-blocker therapy improves LV remodeling, and 3) evaluate whether contractile reserve predicts a favorable response of LV remodeling to beta-blocker therapy. This award, if grant, will allow completion of this project within two years. In addition, the investigator is developing a new method of quantitative assessment of myocardial blood flow reserve ratio by contrast echocardiography using new perfluorocarbon-filled microspheres. This method has been validated in dogs and its validation in humans has recently been funded. The long term goals of the investigator are to use this method to 1) assess the role of microvascular function in the development of clinical CHF and LV remodeling, and 2) evaluate the effect of specific CHF therapies on microvascular function. This work is planned for the later years of this grant proposal after initial validation studies have been completed. Finally, if awarded this grant will allow the investigator to conduct translational research involving the molecular signals for LV remodeling in chronic mitral regurgitation. The long range goals of this project are to identify patients in whom LV failure is imminent for early surgical intervention and to develop therapeutic targets for eccentric LV remodeling in chronic mitral regurgitation and dilated cardiomyopathies.