EFFECTS OF CHRONIC TRTMNT WI BUCINDOLOL HCL OR METOPROLOL TARTRATE

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This study will compare the changes in right ventricular (RV) myocardial gene expression to alterations in ventricular myocardial phenotype in patients with heart failure from idiopathic dilated cardiomyopathy treated for 18 months with either the selective b-blocking agent bucindolol. Changes in gene expression will be related to changes in RV and LV phenotype, as well as to the behavior of the adrenergic and renin angiotensin systems. Gene expression will be measured by quantitative reverse transription-polymerase chain reaction (RT-PCR) estimation of mRNA abundance in total RNA extracted from RV endomyocardial biopsy specimens; ventricular myocardial phenotyping will be by magnetic resonance imaging (MRI), echocardiography, radionuclide ventriculography and cardiac catheterization; adrenergic activity will be directly measured in the heart by isotopic methods; and activity of the renin-angiotensin system will be assessed by measurements of myocardial gene expression and hormonal markers. The objectives of this study are to determine the patterns of gene expression associated with the abnormal human ventricular myocardial phenotype of myocardial failure, and to determine which of these changes in gene expression are under b-adrenergic and renin-angiotensin system control. These objectives will be pursued by comparing gene expression profiles in failing right ventricles studied in this trial vs nonfailing right ventricles assessed in other ongoing studies. In addition, the relationship of changes in gene expression to changes in myocardial phenotype in patients treated for 18 months with either the non-selective b-blocking agent bucindolol or the selective b-blocking agent metoprolol will be assessed.