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.
