LVAD Support Significantly Alters Cardiac Gene Expression Patterns

NEW YORK (Reuters Health) – Results of a study utilizing gene chip technology show that support of the failing human heart with the left ventricular assist device (LVAD) produces significant global changes in myocardial gene expression.

Pre- and post-LVAD hearts demonstrate “significantly distinct genomic footprints,” Dr. Walter J. Koch and colleagues from Duke University in Durham, North Carolina report in the April 2nd issue of the Journal of the American College of Cardiology.

LVAD support in end-stage heart failure can lead to beneficial reverse remodeling of myocardial structure and function, the researchers explain in the paper, but the “molecular mechanisms behind this salutary process are not well understood.”

They analyzed gene expression in paired left ventricular samples from six men obtained during LVAD placement and at the time of explantation. Among roughly 7000 genes, 295 were upregulated and 235 were downregulated following LVAD support.

“The majority of the differential gene expression found consisted of genes not previously known to be affected by LVAD support,” the investigators report. These genes “may provide a host of potentially novel targets for future diagnostic or therapeutic indications,” they predict.

Of interest, the researchers point out, in post-LVAD samples, a “high percentage” of genes involved in metabolism showed “significantly altered expression.” This suggests that “while the heart is mechanically unloaded, the process of reverse remodeling is associated with significant, active changes in cellular metabolic pathways.”

It is also noteworthy, they add, that using a patient’s genomic response to LVAD support, they were able to blindly segregate patients into groups based on heart failure etiology. This finding underscores the “clearly divergent heart failure etiology-specific changes in gene expression.”

In a journal editorial, Dr. Michael R. Bristow of the University of Colorado in Denver notes that this study is “the first report of the application of gene chip technology to measure broad-based gene expression in the setting of LVAD-related effects on the end-stage failing heart.”

“This approach generates a very large amount of data that needs to be vetted, winnowed, and interpreted in some meaningful way,” he writes, adding that an entire subspecialty, that of bioinformatics, was born out of the development of this technology.

J Am Coll Cardiol 2003;1096-1108.