In the early days of his irregular heartbeat, Clarence Mankin would pass out before his implanted defibrillator kicked in to reboot his heart. He would wake up a bit later, dazed but alive. After his doctor adjusted the device’s sensitivity, it would shock his heart before he fainted, which, in some ways, was worse. Mankin could feel it coming — the lightheadedness, the dizziness — and he’d know to brace himself for the jolt.
“It’s like a good thump in the chest. It feels like you are going to die,” he said. “I’d try to grab hold of something, or find something to sit down on, which occasionally I was able to do.”
Mankin, 74, a retired Lutheran pastor in Atlanta, Illinois, used to pride himself on walking 10,000 steps a day, which he tracked with his wrist pedometer. But when he started feeling the jolt all the time — at one point, he was having 11 episodes a day — he stopped walking.
He stopped driving.
He stopped leaving the couch.
About 3 million Americans experience arrhythmia, in which the heart beats too fast, too slow, or too irregularly. One such form, ventricular tachycardia, is the leading cause of sudden cardiac arrest.
An unlikely pairing between a School of Medicine cardiologist and a radiation oncologist, however, has led to a revolutionary treatment: Mankin is one of the earliest patients to sustain a beam of radiation directly to his heart.
Ventricular tachycardia (VT) results from other cardiac problems. Mankin, who served in the U.S. Army during the Vietnam War, had his first heart attack at 44, which he attributed to Agent Orange exposure.
Injury to the heart, commonly from a heart attack, causes some cells to die, forming scar tissue. When heart cells are damaged in this way, they might not function correctly, causing the heart to short-circuit. This makes it beat out of sync, which means the heart might not be able to pump enough blood throughout the body, and it can even stop entirely.
Standard treatments include medications, defibrillators and a procedure known as catheter ablation. Patients must be sedated for this invasive procedure as doctors thread fine tubes through the femoral vein, up into the heart. A tiny electrode tip, no larger than a headphone jack, selectively burns away heart cells that have gone haywire.
The procedure can last from four to 10 hours, and recovery can take several weeks. Although physicians have developed precise ablation techniques to ensure they destroy as many wayward cells as they can, the treatment doesn’t always work. It also has a cluster of side effects, from infections to bleeding problems. In a 2016 study, half of patients who underwent catheter ablation saw their tachycardias return.
The same was true for Mankin.
Then Mankin’s cardiologist referred him to Phillip S. Cuculich, MD, a heart rhythm specialist and an associate professor of medicine at Washington University.
Cuculich and Cliff G. Robinson, MD, an associate professor of radiation oncology, recently had teamed up to provide a new type of arrhythmia treatment, one that cardiologists nationally are calling a game changer for patients with few remaining options.
Mankin agreed to give it a try.
To undergo the procedure, he donned a specially designed vest covered in 252 electrodes (as compared to 12 for a typical electrocardiogram).
Then Cuculich briefly induced VT in Mankin using his defibrillator. This allowed him to produce a panoramic map of Mankin’s heart. Later, Mankin lay inside a cylindrical chamber. A custom mold held him in place to prevent him from moving or breathing too deeply. Robinson used the map to direct an intense, focused beam of radiation at his heart.
The high-energy particle stream is typically used to blast away cancer cells, and, during normal use, Robinson does everything he can to avoid hitting the heart. But this time, his particle beam intentionally zapped malfunctioning cells that were causing Mankin’s heart to beat out of sync.
On average, the procedure takes less than 15 minutes.
“I’ve spent my entire life as a trainee and an attending physician thinking about ways to avoid dosing healthy tissues,” Robinson said. “But this is already an injured region. If you think about it as a diseased part, where Phil would have no problem going in with a catheter to burn that area, well, we are doing the same thing. There are other ways to get energy inside the body.”
Mankin was awake throughout the radiation therapy, which took place Sept. 8 at Barnes-Jewish Hospital. When it was over, he sat up, swung his legs off the table, and walked out of the room. He felt no pain.
On a warm January day, Mankin visited Cuculich’s office for a follow-up appointment. Cuculich downloaded data from his implantable defibrillator, which tracks each time it gives Mankin a jolt. After the appointment, Cuculich printed out the device’s history on a piece of paper, and strode into Robinson’s office in the radiation oncology department.
Early results show that a noninvasive approach is dramatically reducing ventricular tachycardia. (Animation by Mark Hallett.)
“Look at this,” Cuculich said, grinning as he thrust the small square paper into Robinson’s hand. Robinson’s eyes widened: “Wow!” And then the oncologist, still seated in his chair, started dancing.
The sheet of paper was marked with what looked like a bar graph. The bottom axis was time, and the vertical axis depicted every instance the device was activated.
Cuculich pointed out the three months prior to the Sept. 8 radiation treatment. It looked like a forest: A spike each day, some very tall and some shorter, referencing the number of jolts each day from the device. Then Cuculich pointed to Sept. 8, and the months after Mankin’s procedure. The forest had been cleared. The device had not activated
at all. The tachycardia was gone.
Cuculich and Robinson both laughed. “That is amazing,” Robinson said.
More than three months later, Mankin hasn’t had a single jolt from his defibrillator. By February, he was walking 5,000 steps a day. “It’s hard to describe. Now when I walk, I don’t feel like something terrible is going to happen to me,” Mankin said. “I don’t know if this will extend my life or not, but it has made the quality of my life much better.”
When no other options exist
Mankin is one of about two dozen patients enrolled in a clinical trial led by Cuculich and Robinson. The ENCORE-VT trial follows an initial case study from April to November 2015 with just five patients, which the physicians conducted to prove their technique would work. The results were published in The New England Journal of Medicine in January.
Like Mankin, all patients so far have had ventricular tachycardia that has not responded to standard treatments.
In the first clinical trial, the five patients collectively experienced 6,577 episodes of VT in the three months before their radiation treatment. In the nine months afterward, they experienced four.
“It has the potential to benefit a substantial number of people,” said William G. Stevenson, MD, professor of medicine at Vanderbilt University Medical School, who was not involved in the research.
Cuculich spent several years refining techniques to map the heart in four dimensions — the three physical dimensions, plus time — to nail down the precise regions that are malfunctioning. The technique, known as electrocardiographic imaging, was developed by Yoram Rudy, PhD, the Fred Saigh Distinguished Professor of Engineering, director of the Washington University Cardiac Bioelectricity and Arrhythmia Center, and Cuculich’s mentor. But a more detailed picture of heart dysfunction was not enough, Cuculich said.
“Even if you could non-invasively image the heart, we still required entry into the body with a catheter to fix it,” Cuculich said. “It became clear that the place to make an impact was to non-invasively treat it.”
As part of the School of Medicine’s focus on translational research, Cuculich met with neurosurgeon Albert H. Kim, MD, PhD, to discuss using ultrasound technology. Kim recommended Cuculich meet with Robinson. For his part, Robinson was looking for new ways to use stereotactic radiation — a very precise, high-energy dose of radiation — beyond cancer treatment.
“When we first met to discuss this, I was really concerned about how to hit a 5 mm area in a moving, beating heart,” Robinson said. “But Phil’s first question was, ‘How big of an area can you treat?’ And I said, ‘This is going to be a good friendship.’ Because as radiation oncologists, we don’t treat parts of tumors. We treat the whole kit and caboodle.”
Cuculich and Robinson started meeting regularly to discuss each other’s specialties and learn about their patients. Each had to relearn terminology and techniques he hadn’t studied since medical school.
“We have created an entirely non-invasive process to map and treat arrhythmia, and we can do it in less than 10 minutes.”
— Cliff G. Robinson, MD
“That was one of the keys to this initial success, that we came together and talked about it,” Robinson said. “That this could happen is one of the unique things about being at Washington University.”
The physicians developed a technique that relies on multiple imaging methods. MRI, CT and PET scans combine with the electrode vest to produce a detailed map of the heart and pinpoint where arrhythmias are coming from. The imaging process involving patients takes several hours, occasionally spread over multiple days.
“Then Cliff and I sit down together and collaborate over this information, and we come to a conclusion about where the scar is, so we are as precise as possible. We want to avoid any structures that are important to the heart, and keep the potentially damaging energy within the scar,” Cuculich said.
To Robinson, that push and pull — how deep to go, how much tissue to take and how much to leave alone — is much like cancer treatment. Some patients, like Mankin, have large areas that must be treated. The burning tip used in catheter ablation is only about 3.5 millimeters across, roughly the size of a Sharpie tip. In some people, the cells that cause the heart to beat out of sync are not reachable with the tiny catheter tip. This is especially true for cells deep within the heart muscle. The radiation beam can penetrate deeper, targeting all the faulty cells.
Robinson said he was concerned some patients would be fearful of the word “radiation,” but both physicians said their patients have been less resistant than they expected, in some cases because they were desperate for any solution. Mankin said the doctors helped him understand how it would work, and why it could be so effective. “It’s novel, but if you think about it, they’ve been using the gamma knife on cancer surgeries for years now,” he said.
With such a high dose of radiation, even at a very small site, there is a risk of toxicity and ill effects on the surrounding organs and tissues. So far, patients in the initial study and in the ongoing clinical trial have done well, Robinson said. In the initial study, patients reported no complications or pulmonary symptoms during treatment or immediately after. Some people did experience mild inflammation in the lung adjacent to the target, but that resolved within a year, according to the study. Still, the potential long-term effects of the radiation dose are unknown.
“If this is to be used in younger, less-ill patients, the issue of collateral damage will become more relevant,” said Roy John, PhD, professor of medicine at Vanderbilt University Medical Center. He and Stevenson coauthored an editorial explaining the procedure’s potential in The New England Journal of Medicine.
Radiation therapy likely will complement, rather than replace, ablation and other procedures cardiologists have used for many years. It provides another option for VT patients who have exhausted standard therapy options, including catheter ablation, and are facing one-year survival rates below 20 percent.
“When you get complex forms of heart disease that are responsible for a lot of complex circuitry, then there might be an advantage to an approach that is more extensive, rather than precise,” said Francis Marchlinski, MD, director of cardiac electrophysiology at the University of Pennsylvania, who was not involved in the study.
Robinson and Cuculich are finalizing their results from the ENCORE-VT trial, which included 18 patients along with Mankin. Early results, they say, are promising.
“We have created an entirely non-invasive process to map and treat arrhythmia, and we can do it in less than 10 minutes,” Robinson said. “This approach can fundamentally change the way we approach these heart rhythm problems.”
Published in the Summer 2018 issue