New research from the Washington University School of Medicine in St. Louis suggests that radiation therapy can reprogram heart muscle cells to what appear to be a younger state, solving the electrical problems that cause life-threatening arrhythmia without the need for an invasive that has been used for a long time. procedure.
In this invasive procedure – catheter ablation – a catheter is inserted into the heart, and the tissue that triggers the potentially fatal irregular heartbeat – ventricular tachycardia – is burned, creating scars that block stray signals. The new study, however, shows that the non-invasive radiation therapy normally used to treat cancer can reprogram heart muscle cells to a younger and possibly healthier state, solving the electrical problem in the cells themselves without the need. scar tissue to block overactive circuits. The study also suggests that the same cell reprogramming effect could be achieved with lower doses of radiation, opening the door to the possibility of broader uses of radiation therapy in different types of cardiac arrhythmias.
The study appears September 24 in the journal Natural communications.
Researchers at the University of Washington showed in 2017 that radiation therapy usually reserved for cancer treatment could be directed to the heart to treat ventricular tachycardia.
In theory, radiation therapy could mimic the scar tissue usually created by catheter ablation, but with a much shorter and completely non-invasive procedure, making treatment accessible to more seriously ill patients. Surprisingly, doctors found that patients had great improvements in their arrhythmias within days to weeks after radiation therapy, much faster than the months it took for scar tissue to form after radiation therapy, suggesting that a single dose radiation reduces arrhythmia without training. scar tissue. The data indicated that radiation therapy worked as well, if not better, than catheter ablation for some patients with ventricular tachycardia, but in a different and unknown way.
âTraditionally, catheter ablation creates scar tissue to block the electrical circuits that cause ventricular tachycardia,â said senior author and cardiologist Stacey L. Rentschler, MD, PhD, associate professor of medicine, developmental biology and biomedical engineering. “To help us understand if the same thing happened with radiation therapy, some of the first patients to receive this new treatment gave us permission to study their heart tissue – following a heart transplant or if they were had died for another reason e.g. We saw that scar tissue on its own could not explain the remarkable clinical effects, suggesting that radiation improves arrhythmia in another way, so we delved into the details of this . “
Scientists have found that radiation therapy causes heart muscle cells to start expressing different genes. They measured increased activity in a signaling pathway called Notch, known for its vital role in early development, including forming the heart’s electrical conduction system.
Notch is typically turned off in adult heart muscle cells. But the researchers found that a single dose of radiation temporarily activates Notch signaling, leading to a long-term increase in sodium ion channels in heart muscle, a key physiological change that can reduce arrhythmias.
âArrhythmias are associated with slow electrical conduction velocities,â Rentschler said. “Radiation therapy appears to speed up the pace by activating early developmental pathways that return heart tissue to a healthier state.”
Researchers studied these effects in mice and in individual human hearts. In human heart samples, the researchers found that these changes in heart muscle cells were only present in areas of the heart that received the targeted dose of radiation.
“Radiation therapy causes one type of injury, but it’s different from catheter ablation,” said co-author and radiation oncologist Julie K. Schwarz, MD, PhD, professor of radiation oncology and division director of cancer biology from the radiotherapy department. Oncology. âAs part of the body’s response to this injury, cells in the injured part of the heart seem to activate some of these early developmental programs to repair themselves. It is important to understand how this works because with this knowledge we can improve the way we treat these patients and then apply it to other diseases. “
The researchers also found that the beneficial effects of radiation continued for at least two years in surviving patients. Most importantly, they were able to demonstrate in mice that a lower dose of radiation produced the same effect. A lower dose of radiation could minimize long-term side effects and open the door to this type of treatment in other types of cardiac arrhythmias. And while Notch was a big player in those effects, Schwarz said it wasn’t the only path involved. Researchers continue to study how radiation causes heart cells to return to a healthier state.
First author David M. Zhang, medical / doctoral student at Rentschler’s lab, added: âIt has been an exciting collaboration not only between basic scientists and clinicians, but also cardiologists and radiation oncologists. Historically, radiation oncologists have focused on cancer and try to avoid irradiating the heart, so this study opens up a whole new area of ââresearch and collaboration between these two areas. “
This work was supported by the National Institutes of Health (NIH), grant numbers T32 HL134635, T32 GM07200, R01 HL130212, UH3 HL141800, and S10 OD020136. This study received seed funding from the Department of Radiation Oncology, Division of Cancer Biology, at the University of Washington. Schwarz holds an AACR-Bristol Meyers Squibb Female Researcher Award and funding from the Radiological Society of North America. Rentschler holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and funding from the Foundation for Barnes-Jewish Hospital which directly supported this work.
University of Washington co-authors Clifford Robinson, MD, and Phillip Cuculich, MD, have filed two patents owned by the institution: Non-invasive Imaging and Treatment System for Cardiac Arrhythmias which relates to comprehensive methods of administration of cardiac radiation to the patient; and A system and method for determining segments for ablation that relate to the use of cardiac segments for targeting cardiac radiation. They also provide consulting services to Varian, which produces linear accelerators for the delivery of radiation therapy treatments.