Does combination therapy with LVAD and clenbuterol alter specific gene expression pathways associated with ventricular recovery in patients with end-stage heart failure?
Functional recovery in end-stage heart failure following LVAD and clenbuterol therapy is associated with integrin pathway signaling and down-regulation of EPAC2.
AIMS: A novel combination therapy consisting of a left ventricular assist device (LVAD) combined with pharmacologic therapy including the selective beta(2)-agonist, clenbuterol, has shown promise in restoring ventricular function in patients with heart failure. The aim of this study was to identify common genes and signalling pathways whose expression was associated with reversal of heart failure and restoration of ventricular function. METHODS AND RESULTS: Microarray analysis was performed on six paired human heart samples harvested at the time of LVAD implant and at the time of LVAD explant for recovery of ventricular function (post). Follow-up data shows that the improvements in ventricular function have been maintained for an average of 3.8 years post-explant. Analysis of the gene expression data revealed: (i) a significant association of integrin pathway signalling with recovery and (ii) the identification of several novel targets including, EPAC2, in the well-described cAMP pathway whose expression was down-regulated with recovery, and was associated with improvements in cardiac contractility, metabolism, and function. CONCLUSION: This data set represents the first description of signalling pathways associated with the functional recovery of end-stage human heart failure and the identification of new targets in the human heart that are modified by this combination therapy.
Hall et al. (2006) studied this question.