In an effort to better manage patients with life-threatening irregular heartbeats who have exhausted all other treatment options, doctors are irradiating the heart.
Despite the fact that it is highly experimental, initial research reveals that it may reprogram misfiring cardiac cells to regulate heartbeats more like younger, healthier cells.
Dr. Stacey Rentschler of Washington University in St. Louis said, “It may actually rejuvenate diseased tissue, which is very exciting.”
The irregular heartbeat known as ventricular tachycardia is a leading cause of sudden cardiac arrest, accounting for approximately 300,000 annual fatalities in the United States. Radiation therapy is a radical approach; oncologists are trained to avoid irradiating the heart out of concern for collateral harm.
Now, scientists are about to launch the first rigorous study to determine if a fast, one-time dose to combat this irregular heartbeat works well enough — and is safe enough — for additional patients like Jeff Backus, who relapsed after receiving standard treatment.
The Louisville man had already undergone a lengthy invasive procedure and had a defibrillator implanted to maintain his heart beating normally. This winter, Backus fainted twice within a month and awoke to feel as if he had been kicked in the thorax. The defibrillator had to shock his heart back into rhythm in order to save him.
“In the back of your mind, you constantly wonder, ‘Is it going to happen?'” Backus said. In February, he chose experimental radiation to prevent a recurrence of the terrifying episode because he had exhausted all other options. So far, he is doing well. “It gave me some hope.”
The electrical system of the heart normally causes it to pulse between 60 and 100 times per minute. Ventricular tachycardia is an abnormally rapid heartbeat that cannot effectively circulate blood. It occurs when these electrical signals short-circuit in the ventricles, usually due to injury from a previous heart attack.
The primary treatment consists of inserting catheters into the heart to identify and burn misfiring tissue, thereby creating scars that block poor signals. Some patients are too ill for this “catheter ablation”, and for others, such as Backus, the problem ultimately returns.
Dr. Phillip Cuculich, a specialist in cardiac rhythm at Washington University, conceived of a non-invasive alternative.
It requires a great deal of initial experimentation. In order to measure the electrical activity of the heart, patients wear a garment with approximately 250 electrodes, as opposed to the standard dozen. Combined with comprehensive medical scans, this provides Cuculich with a three-dimensional map pinpointing the location of the irregular heartbeat.
How can I get there? Cuculich collaborated with Dr. Clifford Robinson, an expert in precisely targeted radiation to combat cancer while avoiding healthy tissue.
Targeting the emotions was not at all on my radar. My objective was to avoid the heart,” said Robinson. In fact, some survivors of lung and breast cancer develop heart disease years later due to tumor radiation that reached and inflames cardiac tissue.
However, he agreed to attempt, cautioning patients of potential long-term risks. His very first arrhythmia patient replied, “You’re worried about something that might occur in 10 or 20 years? “I’m concerned about tomorrow,” recalled Robinson. This was extremely enlightening.
Patients recline in the same machine that is typically used to destroy cancer while listening to music and receiving targeted beams of radiation. It can be completed within 15 minutes.
In 2017 and 2019, Cuculich and Robinson reported their first successes with experiments involving a small number of critically ill patients who exhibited dramatic improvement. Some are reportedly doing well up to six years later.
While not certified by the Food and Drug Administration, the duo has since received permission to treat about 80 additional patients on an individual basis, including Backus, who was not as ill as the initial patients. In addition, the St. Louis team has taught the technique to dozens of hospitals in the United States and abroad that are cautiously attempting it.
However, the FDA requires stronger evidence for routine use, and the more hospitals that provide “off-label” radiation to these cardiac patients, the more difficult it will be to obtain this evidence.
Now, in a global study sponsored by the medical device manufacturer Varian, nearly 400 patients will be randomly assigned to either radiation or another catheter ablation in order to directly compare their outcomes. Washington University has just started recruiting potential participants; additional sites will shortly be opening.
The greater enigma is how radiation prevents arrhythmias. Cuculich believed it would work by simply duplicating the scarring caused by catheter ablation, but was astonished when scans revealed: “We weren’t actually causing a new scar — and that’s a big deal.”
Rentschler, a developmental biologist who also treats cardiac patients, inspected the specimen in greater detail. Tests on donated human and mouse hearts indicate that the one-time moderate dose of radiation prompted the misfiring cells to repair.
In zapped regions, heart muscle cells temporarily activated genes that are normally quiescent in adulthood. Among them is the “Notch” signaling pathway, which aids in the formation of the developing heart’s electrical system.
Rentschler explained that reactivating this pathway “awakens these regions” so that they conduct electrical signals more like when they were younger. There has never been a treatment that could accomplish that.
This is very distinct from how repeated doses of radiation can eradicate tumors. Now, Dr. Rentschler’s research team is examining human cardiac cells in Petri dishes, measuring how they conduct electrical impulses with the hope that even lower radiation doses may be effective.
“It’s crucial that we get this right…that we determine what the safe doses are and whether there are any areas of concern,” Cuculich said.
