The long-term goal of this research proposal is to define a time for surgery in chronic left ventricular (LV) volume overload resulting from aortic regurgitation (AR) or mitral regurgitation (MR) to preserve or restore normal LV size and performance. The natural history of LV volume overload follows a potentially identifiable hemodynamic course characterized by compensated LV hypertrophy, followed by LV systolic dysfunction in the absence of myocardial dysfunction, and finally, irreversible myocardial dysfunction. The commonly employed clinical, non- invasive, and invasive indices tend to identify patient with AR and MR late in their hemodynamic course when irreversible myocardial dysfunction predominates. In contrast, the preliminary data from this laboratory strongly support the hypotheses that LV systolic dysfunction in the absence of myocardial dysfunction can be identified in patients with AR and MR by applying both the maximum time-varying elastance and myocardial stiffness concepts, that LV systolic dysfunction in this setting is the result of inadequate LV hypertrophy and assumption of spherical geometry, and that surgery for LV volume overload at this time will reverse these detrimental hemodynamic processes and, thereby, preserve or restore normal LV size and performance. Therefore, the specific aims of this research proposal are: 1) to characterize LV chamber performance and myocardial properties using the time-varying elastance and myocardial stiffness concepts in normal patients and contrast them with those in patients with AR or MR; 2) to establish mechanisms for abnormal LV chamber elastance in the presence of normal myocardial properties; 3) to establish subgroups of patients with AR or MR based upon the presence or absence or normal LV chamber elastance and myocardial properties; 4) to define the extent and time course of changes in LV size and performance during the year following surgery for AR and MR, and 5) to characterize the independent effects of surgery for AR and MR on LV chamber elastance and myocardial properties. This research proposal represents, therefore, a unique combination of sophisticated hemodynamic approaches that are integrated to focus on providing new data to define the mechanisms for LV systolic dysfunction in the absence of myocardial dysfunction and a time for surgery in patients with AR and MR to preserve or restore normal LV size and performance.
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