Left ventricular assist device-induced molecular changes in the failing myocardium.
OBJECTIVE
There is considerable increase in the use of left ventricular assist devices for the treatment of severe heart failure. Traditionally viewed as a bridge to transplantation and more recently as a destination therapy, left ventricular assist device support is now recognized to offer potential for myocardial recovery through reverse remodeling, a potential that is further enhanced by combination with pharmacologic therapy. In this study, we examine the molecular changes associated with left ventricular assist device support and how these may contribute to the recovery process.


RESULTS
Studies in both patients and experimental models have demonstrated that improved function is associated with alterations in several key pathways including cell survival, cytokine signaling, calcium handling, adrenergic receptor signaling, cytoskeletal and contractile proteins, energy metabolism, extracellular matrix, and endothelial and microvascular functions. Moreover, the unique research opportunities offered by left ventricular assist device analysis are beginning to distinguish changes associated with recovery from those of mechanical unloading alone and identify potential predictors and novel therapeutic targets capable of enhancing myocardial repair.


CONCLUSIONS
Significant progress has been made toward revealing molecular changes associated with myocardial recovery from heart failure. These studies also offer new insight into the pathogenesis of heart failure and point to novel therapeutic strategies.
Soppa
Gopal K R
GK
Imperial College London, NHLI, Heart Science Centre, Harefield Hospital, Harefield, UK.
Barton
Paul J R
PJ
Terracciano
Cesare M N
CM
Yacoub
Magdi H
MH
D000818:Animals; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism; D015398:Signal Transduction; D020257:Ventricular Remodeling