Abstract 14981: Altered Gene Expression in Diabetic Heart Failure Patients

Abstract

Introduction: Diabetes and heart failure are very closely associated. Diabetes patients have an increased risk of developing heart failure and heart failure patients are at higher risk of developing diabetes. Changes occur in myocardial glucose metabolism in end stage heart failure patients and newer therapies for diabetes such as SGLTi improve heart failure outcomes. Our objective was to identify transcriptional changes associated with diabetes in heart failure patients. Methods: Transcriptional profiles were compared in heart tissues obtained at the time of LVAD implant among diabetic heart failure (HF) (n=16), non-diabetic (n=10) HF patients and control (n=3) non failing hearts. RNASeq analysis utilized a custom-targeted panel for 140 genes on the Ion Torrent Personal Genome Machine. Coverage analysis as well as mapping the reads and alignment was done using the Ion Torrent Browser SuiteTM. The Bejamini-Hochberg method was used to control the false discovery rate to be no more than 0.05. Ingenuity Pathway Analysis (IPA) was also performed to understand the biological pathways involved. Results: Our sample population was 82% male with an average age of 51 and 84% Caucasian, 14% African American and 2% Asian. Average ejection fraction was quite low <25% and average NYHA was 3.5 in the HF populations. Expressions of contractile muscle and ion channels proteins decreased significantly between HF patients and control. Increased expression of chemokine ligand 4 (CCL4), chemokine ligand 2 (CCL2) and collagen type 1 alpha1 (COL1A1) were observed in diabetic HF compared to non-diabetic HF patients. IPA analysis with log fold change between HF and control revealed activation of both methylation genes DNMT3A and B, necrosis of cardiac muscle and death of cardiomyocytes with 2.0 Z score. Conclusions: Diabetic heart failure patients have increased expression of chemokines and extracellular matrix genes, which may contribute to disease progression. Up regulation of CCL4 and CCL2 in diabetic HF patients may cause additional risk of heart diseases through inflammatory pathways and increased expression of collagen may contribute to myocardial fibrosis. Down regulation of contractile proteins, and ion channels were similar in diabetic and non-diabetic HF patients.