Migration of Native Bone Marrow Cells to the Heart in Acute Non-Ischemic Cardiomyopathy

poorly understood. The goal of this study was to evaluate changes in gene expression associated with improvement in cardiac function on beta-blocker therapy. Methods: This is a randomized multicenter trial involving fifty patients with idiopathic dilated cardiomyopathy. Patients were randomized to metoprolol, metoprolol + doxazosin, or carvedilol in a 1:1:1 fashion. At baseline, 3 months, and 12 months patients had endomyocardial biopsies done for serial analysis of myocardial gene expression measurements. Left ventricular ejection fraction (LVEF) was measured by radionuclide ventriculography. Fifty genes previously associated with heart failure were evaluated by microarray. Analysis was conducted in SAS with a p ! .05 considered significant. Results: Baseline patient characteristics included: LVEF5 276 11%; mean age 45.66 13 years, percent male 74%, percent Caucasian 70%. LVEF improved on average by 11% at 3 months and 16% at 12 months. Conclusions: The transcriptional changes associated with reverse cardiac remodeling on beta-blockers are complex. They involve adrenergic and angiotensin signaling, natriuretic peptides, calcium handling and sarcomeric proteins. Reverse remodeling is associated with up-regulation of myocardial beta-1, beta-2, and alpha-1C adrenergic receptors. It is also clearly linked with a down regulation of brain and atrial natriuretic peptides as well as angiotensin I converting enzyme and endothelin-1. Beta-blockers reverse isoform shifts in sarcomeric proteins, down-regulating troponin I type 3 while increasing alpha-myosin heavy chain. In addition reverse remodeling involves up-regulation of phospholamban and voltage dependent calcium channels.