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Mechanical Heart Pump Alters Gene Activity
By Adam Marcus

Some patients treated for heart failure receive a mechanical pump to stimulate the heart’s left ventricle, the chamber that pumps blood throughout the body. The device can lead to structural improvements in heart muscle, a process known as remodeling.

To learn about how remodeling occurs, researchers at Duke University Medical Center in Durham, North Carolina, have used genomic tools to study heart cells before and after the implant surgery. They found a distinct pattern of gene activity—a gene signature—associated with remodeling.

Left ventricular assist device, or LVAD.

Specifically, 530 genes were either more or less active following the implant surgery compared to before the surgery. The data, from the study’s six patients, provide an overview of the genetics of remodeling. Understanding how the device contributes to remodeling could lead to better devices and therapies.

The researchers also found that the six patients could be divided into two groups based on their type of heart failure and their gene signatures. Three of the patients had a signature that correlated with the ischemic form of heart failure, in which heart cells die from lack of blood flow.

"We saw clear differences in gene expression" depending on whether the patient’s heart failed due to the ischemic form of cardiomyopathy, or the non-ischemic form, says Walter Koch, a member of the Duke team.

The mechanical pump is called a left ventricular assist device, or LVAD. The device is considered a "bridge" to heart transplantation surgery, but at least some patients have been able to avoid a transplant because their hearts regained sufficient function while using the device.

With more studies like this one, researchers could begin to identify gene signatures that correlate with successful outcomes following surgery, allowing doctors to identify patients who will do well with the device. The number of people needing donated hearts far exceeds the available organs.

"The ultimate goal is to predict, based on a person’s gene profile, how they would do with LVAD as therapy and not as a bridge to transplant," says Koch. The study appears in the Journal of the American College of Cardiology.

The Duke team analyzed the heart cells using “gene chips,” which are devices that containing DNA from thousands of genes—in this case 6,800 genes. Also known as DNA microarrays, gene chips tell researchers which genes are switching on and off in a cell.

Michael Bristow, head of cardiology at the University of Colorado Hospital in Denver, calls the latest study "intriguing but preliminary." Bristow, author of an editorial accompanying the study, says scientists now need to determine which genes are most important to remodeling and heart failure.

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Blaxall, B.C. et al. Differential gene expression and genomic patient stratification following left ventricular assist device support. J Am Coll Cardiol 41 (April 2, 2003).

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