Reverse Remodelling and Recovery from Heart Failure Are Associated with Complex Patterns of Gene Expression

Combined left ventricular assist device (LVAD) support and pharmacological management of the failing heart can induce reversal of maladaptive cardiac remodelling leading to normalisation of cardiac structure and recovery of cardiac function. The purpose of this study was to compare the gene expression profiles of recovered and non-recovered LVAD patients in order to identify mechanisms underlying the recovery process and differences which may determine outcome. Myocardial expression of 54 genes chosen for their potential role in heart failure and tissue repair was measured using quantitative PCR at the time of LVAD implantation and again at explantation (recovery, n = 13) or transplantation (non-recovery, n = 5). Patients who went on to recover had higher levels of Gi alpha 2, EPAC2 and lower levels of IGF2 at the time of LVAD implant compared to patients who failed to recover. During recovery, expression of BNP, IL-1 beta, VWF and SFRP1 was decreased whilst RGS4 increased. Expression of IGF1 and pro-fibrotic genes was coordinated during recovery. Correlation analysis identified a novel co-regulation of SFRP1 and beta MHC in myocardium. In summary, the gene expression profile underlying recovery is complex and comprises both regression and exacerbation of elements of the pathological gene program. Modulation of Gi alpha 2, EPAC2, RGS4 and SFRP1 indicates that inhibition of cAMP signalling may potentiate recovery prior to treatment whilst enhanced cAMP and Wnt signalling may underlie recovery during LVAD support.