Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy.
OBJECTIVE
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.


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.


CONCLUSIONS
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
Jennifer L
JL
Lillehei Heart Institute, Division of Cardiology, Department of Medicine, University of Minnesota, Mayo Mail Code 508, 420 Delaware Street SE, Minneapolis, MN 55455, USA. jlhall@umn.edu
Birks
Emma J
EJ
Grindle
Suzanne
S
Cullen
Martin E
ME
Barton
Paul J
PJ
Rider
James E
JE
Lee
Sangjin
S
Harwalker
Subash
S
Mariash
Ami
A
Adhikari
Neeta
N
Charles
Nathan J
NJ
Felkin
Leanne E
LE
Polster
Sean
S
George
Robert S
RS
Miller
Leslie W
LW
Yacoub
Magdi H
MH
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000318:Adrenergic beta-Agonists