Therapeutic radiation is typically reserved for cancer treatment, but scientists at Washington University School of Medicine in St. Louis have applied radiation therapy to treat ventricular tachycardia, a life-threatening heart arrhythmia. A news release issued by the university says that the results of the study show that radiation therapy can “reprogram” heart muscle cells to “a younger and perhaps healthier state.” The findings were published in the journal Nature Communications on September 24.
The current standard treatment for ventricular tachycardia is catheter ablation, an invasive procedure that involves threading a catheter into the heart and burning the tissue responsible for sending irregular electrical signals. Over a few months, scar tissue develops in the treated region, blocking those signals. Research published in 2017, also from Washington University in St. Louis, found that patients treated with radiation showed improvement within days or weeks, which led physician-scientists to believe that a different mechanism might be behind the beneficial effects of radiation therapy.
The findings: The researchers studied these effects in mice and in the donated hearts of patients who had undergone radiation therapy. They found that radiation treatment triggered heart muscle cells to begin expressing different genes. A signaling pathway called Notch, which is involved in forming the heart’s electrical conduction system and is typically “switched off” in adult heart muscle cells, showed increased activity. The temporary radiation-induced activation of Notch signaling lead to a long-term increase in sodium ion channels in the heart muscle, reducing arrhythmias.
“Arrhythmias are associated with slow electrical conduction speeds,” said senior author and cardiologist Stacey L. Rentschler, associate professor of medicine, developmental biology, and biomedical engineering. “Radiation therapy seems to kick up the speed faster by activating early developmental pathways that revert the heart tissue back into a healthier state.”
Self-repair: In the human heart samples, the researchers found that the changes in heart muscle cells were present only in areas of the heart that had received the targeted radiation dose. The researchers also found that radiation treatment worked just as well or better than catheter ablation, and that the beneficial effects of radiation continued for at least two years in surviving patients. In addition, they were able to demonstrate in mice that a lower dose of radiation produced the same effect.
“Radiation does cause a type of injury, but it’s different from catheter ablation,” said study coauthor and radiation oncologist Julie K. Schwarz, professor of radiation oncology and director of the Cancer Biology Division in the Department of Radiation Oncology. “As part of the body’s response to that injury, cells in the injured portion of the heart appear to turn on some of these early developmental programs to repair themselves. It’s important to understand how this works because, with that knowledge, we can improve the way we’re treating these patients and then apply it to other diseases.”