Comprehensive Analysis of Differential Expressed Genes Related with Myocardial Reverse Remodeling Following HeartWare Ventricular Assist Device Implantation

Purpose Clinical and experimental studies have suggested that the powerful mechanical unloading effects caused by left ventricular assist device (LVAD) may induce reverse remodeling of the failing heart. However, the detailed mechanism and process have not been fully elucidated. Recent advances in next generation sequencing has enhanced transcriptomic analysis to quantify gene expression extensively. We aimed to characterize gene expression profiling related with left ventricle (LV) reverse remodeling in failing human heart, before and after HeartWare LVAD (HVAD) implant. Methods Sequencing-based comprehensive analysis of gene expression profiling was performed through next generation sequencing in paired human failing LV samples (n=5; median age, 54 years; 4 men) collected pre- and post- HVAD, as well as non-failing human LV collected from donors (n=8, median age, 41 years; 3 men). Results Overall, mapping of sequencing reads corresponded to 48,162 genes in these human LV samples. Among them, 9,094 differentially expressed genes were found in pre- HVAD compared with non-failing LV, while 6,788 differentially expressed genes were detected in post- HVAD compared with non-failing LV (Figure). The discrepancy in the number of differentially expressed genes between pre- and post- HVAD is associated with the effect caused by HVAD. Furthermore, paired analysis performed between pre- and post- HVAD suggest serum amyloid A1 may contribute a major mechanism of LV reverse remodeling. Conclusion Our proposed analysis identified that the gene expression profiling was markedly influenced in response to HVAD. These results suggest that the altered genes expression during HVAD implantation may play important role in the pathogenesis of heart failure and reverse remodeling.