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Radiation therapy triggers genes that heal the heart

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A new study investigates radiation therapy as a noninvasive treatment for heart failure-related arrhythmias. Sviatlana Lazarenka/Getty Images
  • Heart failure is a leading cause of death globally.
  • A type of arrhythmia called ventricular tachycardia is a common cause of death in people with heart failure.
  • Existing procedures to treat heart arrhythmias in individuals with heart failure can be invasive and variable in their success.
  • A recent study suggests noninvasive radiotherapy might help treat arrhythmias by triggering genes that can improve electrical conduction in the heart.

Pioneering research suggests radiotherapy triggers gene expression in the cells of damaged heart tissue to improve electrical conduction.

Health experts could use this discovery to treat patients with heart failure due to ventricular tachycardia, a condition that causes heartbeat disruption.

The Centers for Disease Control and Prevention (CDC) state that over 6 million people have heart failure in the United States. Additionally, up to 4 out of 5 individuals with heart failure have episodes of ventricular tachycardia.

Ventricular tachycardia refers to a fast, atypical heart rate that starts in the ventricles of the heart. It can be life threatening.

Often, doctors treat ventricular tachycardia using invasive radiofrequency catheter ablation. This procedure involves inserting electrode catheters into a vein or artery and guiding them to the heart. Once in the heart, they destroy damaged heart tissue using radiofrequency energy.

Experts assumed this procedure works by blocking the errant electrical signals by creating scar tissue.

However, previous studies show that when healthcare professionals used radiotherapy to treat ventricular tachycardia, patients improved quicker than expected if scar formation was the underlying mechanism.

They often benefited within weeks rather than months, which is how long it would take for heart tissue to scar. This implies that scar tissue may not tell the whole story.

Now, a study in Nature Communications demonstrates that radiotherapy treatment does indeed work in a different, unexpected way.

To determine why people with ventricular tachycardia improve so much quicker than expected, researchers at the Washington University School of Medicine in St. Louis, MO, carried out a series of experiments on humans, mice, and donated heart tissue.

They found that four people who had undergone radiotherapy to treat heart arrhythmias showed improvement 6 months after the procedure but had no significant increase in scar tissue at the radiotherapy site.

The scientists also carried out RNA sequencing on the heart tissue of mice that had radiotherapy exposure. From this, they showed that the radiotherapy treatment activated genes responsible for a particular signaling pathway.

This signaling pathway, called Notch, is involved in early development. Among other tasks, it helps control the formation of the heart’s electrical conduction system.

That Notch is activated is surprising. Scientists did not think these genes were active in adult heart cells — just during heart development.

“Arrhythmias are associated with slow electrical conduction speeds,” says senior author Dr. Stacey L. Rentschler, Ph.D. “Radiation therapy seems to kick up the speed faster by activating early developmental pathways that revert the heart tissue back into a healthier state.”

In mouse experiments, the scientists showed that the benefits of radiotherapy were effective even at a lower dose.

This might mean that noninvasive radiotherapy — similar to that given to people with cancer — could replace the invasive radiofrequency catheter ablation technique.

Dr. Shephal Doshi, director of cardiac electrophysiology and pacing at Providence Saint John’s Health Center in Santa Monica, CA, has described the research as “unique.”

He told Medical News Today that it was good to have some data to support discussion around using radiotherapy to treat patients with arrhythmias: “It is not a new concept, but it has taken a long time to have any kind of meaningful clinical data.

“Obviously, as we all get more advanced, we want to live a life like Star Trek, right? Where you can just kind of point something at the chest and suddenly, without cutting somebody open and putting catheters in, the heart will fix. We are far from being ready to do any kind of clinical trial or study yet, but we are heading in that direction.”

He also pointed out that the study had not shown whether changing electrical conduction in the heart had actually improved survival. He said the next step would be to create a model where researchers could investigate this question.

MNT also spoke with Dr. Aitor Aguirre, assistant professor of biomedical engineering at Michigan State University in East Lansing, who has developed self-assembling heart organoids to investigate cardiac development.

He suggested that scientists need to examine the mechanism behind these discoveries next.

He also told MNT that the findings revealed the possibility of cell programming mechanisms we are unaware of:

“It is a very, very interesting observation, in my opinion, to see that reprogramming can occur in vivo — inside of a living heart — in response to an external cue like radiation, for example.”

“We know [cells] can reprogram in people — we don’t know exactly the mechanisms, the context, and we don’t know why. The heart is very poorly understood, so it is very interesting to see that the heart can mount a reprogram response in response to radiation.”

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