Abstract 3760: Genomic Determinants of Recovery of Normal Ventricular Function in Patients with Dilated Cardiomyopathy
Recovery of normal ventricular systolic function with medical therapy is seen with increasing frequency in patients with dilated cardiomyopathy (DCM). Our laboratory has previously described clinical and demographic features associated with recovery of normal ventricular function. To examine possible genomic determinants of restoration of normal ventricular function, DNA was obtained from 58 patients with DCM who regained normal ventricular function with medical therapy alone and 116 patients who did not and who were frequency matched based on initial ejection fraction. A panel of 14 polymorphic variations of genes known to influence cardiovascular function were examined in these two cohorts. Stepwise logistic regression analysis with forward selection was performed to identify polymorphisms associated with recovery of ventricular function. The two patient groups were exactly matched with a baseline ejection fraction of 19 ± 7 % and the ejection fraction in the recovered group significantly (p < 0.0005) increased to 51 ± 9 %. Of the 14 polymorphisms, four were included in the final logistic regression model (Table⇓) and consisted of genomic variations in adenosine monophosphate deaminase 1 (AMPD1), an exonic variation in endothelial nitric oxide synthase (ENOS3), a promoter polymorphism of monocyte chemoattractant protein 1 (MCP-1), and a microsatteline polymorphism of heme oxygenase 1 (HO). Three of these polymorphisms are related to regulation of oxidant mediated and inflammatory pathways, and AMPD-1 has been previously shown to be associated with greater transplant free survival. Detection of these polymorphisms may identify patients who are likely to respond to standard medical therapy alone without more advanced therapies such as bi-ventricular pacing or cardiac transplantation. These findings provide a pharmacogenomic basis for novel therapies targeted at complete restoration of normal ventricular function in patients with DCM.