We sought to determine whether mechanical unloading of the failing human heart with
a left ventricular assist device (LVAD) results in significant changes in overall
left ventricular gene expression.
Mechanical circulatory support by LVAD in end-stage human heart failure (HF) can result
in beneficial reverse remodeling of myocardial structure and function. The molecular
mechanisms behind this salutary process are not well understood.
Left ventricular samples from six male patients were harvested during LVAD placement
and subsequently at the time of explantation. Cardiac gene expression was determined
using oligonucleotide microarrays.
Paired t test analysis revealed numerous genes that were regulated in a statistically
significant fashion, including the downregulation of several previously studied genes.
Further statistical analysis revealed that the overall gene expression profiles could
significantly distinguish pre- and post-LVAD status. Interestingly, the data also
identified two distinct groups among the pre-LVAD failing hearts, in which there was
blind segregation of patients based on HF etiology. In addition to the substantial
divergence in genomic profiles for these two HF groups, there were significant differences
in their corresponding LVAD-mediated regulation of gene expression.
Support with an LVAD in HF induces significant changes in myocardial gene expression,
as pre- and post-LVAD hearts demonstrate significantly distinct genomic footprints.
Thus, reverse remodeling is associated with a specific pattern of gene expression.
Moreover, we found that deoxyribonucleic acid microarray technology could distinguish,
in a blind manner, patients with different HF etiologies. Expansion of this study
and further development of these statistical methods may facilitate prognostic prediction
of the individual patient response to LVAD support.