"The goal is to treat patients with life-threatening VT in a safer, faster and a better way," explained Cuculich. "The goal is to recreate what we in the heart with catheters, but rather than going into the body, we leverage the technology that Cliff and his radiation oncology team do everyday to treat lung tumors. So instead of treating a tumor, we want to treat the scarred part of the heart with focused radiation. That procedure only takes 7-10 minutes while the patients are awake and listening to music, and it is not painful. So the experience is better for the patient rather than a seven-hour catheter ablation and an overnight stay, and possibly multiple days at the hospital. Instead, this is turned into an outpatient procedure."

He said treating this high-mortality population with radiation therapy was able to extend the life of most patients in the study.

The reaction to this trial has been very enthusiastic. 

"When you talk to the EPs here at HRS, they are by and large super enthusiastic, because they see this could be a great leap forward," Cuculich said. 

Survival was extended out an average of 31 months for severe VT patients

The 19 patients in the study primarily presented with NYHA class 3-4 heart failure. Their mean left ventricular ejection fraction (LVEF) was 25%, and they had VT storm despite the use of amiodarone. These patients also had at least one prior catheter ablation procedure. All patients had ICDs that were shocking the patients on a regular basis. Median follow-up of living patients was six years.

The study found recurrent VT was common in radiotherapy ablation patients, but ICD shocks were rare compared to six months before treatment. Median ICD shocks per six-month period decreased from four before treatment to zero for every timeframe after treatment. Freedom from ICD shock was 72% at 1 year. However, freedom from any VT during follow-up was 13%.

During the follow-up period, 15 patients died. However, median survival in this high-mortality population was 31 months (95% CI, 8.3-58.1). Also, 1-, 2-, and 5-year survival were 74%, 53% and 25%, respectively. The cause of death for these participants was determined to be cardiac failure (38%) noncardiac (31%), cardiac-arrhythmic (25%), and unknown (6%).

Cuculich said the patients enrolled in the study were very sick and the standard of care to try and stabilize their condition did not work, so generally these patients would have a very high mortality rate. 

"They were not really meant to live long in that condition. And yet, by delivering this 7-10 minute noninvasive treatment, we saw an average of 31 months for survival."

Radiation therapy to ablate the heart is new territory with unknowns

In radiation oncology, the heart is an organ oncologists try to avoid completely or minimize exposure to avoid potential damage. So deliberately targeting the heart with radiation has been a methodical research process to better understand what the heart can tolerate and what can go wrong.

Radiation-related serious adverse events occurred in four or the 19 patients. These included pericarditis, pericardial effusion, gastro-pericardial fistula and severe mitral regurgitation. Cuculich said the four cases of pericarditis and pericardial effusion were managed with medication. One patient who had a worsening of mitral regurgitation was treated with a transcatheter MitraClip procedure. 

The most serious adverse event was one case of gastro-pericardial fistula, which appeared three years after treatment and required an urgent surgical repair. Cuculich said the patient went on to live several more years.

The fistula was a learning experience and modifications were made to future ablation treatment plans. Since then, an additional 50-60 VT ablations have been performed with no additional fistulas, Cuculich said.

"The use of high-dose precision radiation has been around for decades, but it has not been routinely employed specifically in this area," Robinson said. "But with that said, what is very clear, if you see a side effect or have an adverse event, the idea is not to then say we cannot do it anymore. You learn and you adapt. And with some minor modifications, you can scoot the dose into that area you need it. We also need to modify how we think about breathing, and how we think about fasting before treatment. I think it will be unlikely that we will see something like the fistula again."

He said it is very important to follow patients out for years in these types of studies because with radiation, it can take many years before an issue shows up.

How radiotherapy ablation of the heart works

In traditional VT ablation, an EP uses an invasive mapping catheter to create an electrical activation map of the heart to try and pinpoint the source of the VT. Then an invasive ablation catheter is used to destroy the heart cells causing the arrhythmia. These procedures take hours to perform.

With noninvasive radiotherapy EP ablation, Cuculich said computed tomography (CT) can image areas of scarring that cause VT in the myocardium of the ventricle. In additional, noninvasive ECG mapping techniques can show electrical activity in the myocardium and be overlaid on the CT scan to narrow down the target area of the ablation. 

CT scans are used in radiation oncology to develop a treatment plan used by the therapy system to deliver doses of radiation. The Hounsfield units that create the different levels of grayscale pixels that make up CT images have a direct correlation to the electron density of tissues they represent. This is used to calculate the radiation energy levels needed to deliver a specific radiation dose to a target inside the body. 

The overlay of the electrical mapping information is similar to the overlay of nuclear imaging on CT that are often used to target tumors in radiation oncology.

"From the patient standpoint, it is nice to have a few pictures of the heart and then have a treatment that you can have and get up and leave as an outpatient," Cuculich said. "It has really changed the paradigm of what it is like to be a patient with VT. When you talk to the patients, they feel like it is a really amazing evolution." 

Robinson said he appreciates the collaboration with EP because it is combining the expertise from two specialities to better care for patients.

"It is essentially mutually beneficial endpoint, because we have these patients who are the most challenging. These are the ones where I see Phil come back at the end of the day after a long day in the lab and he is exhausted and maybe it still did not work. For the radiation oncologists, this is a brand new population we are working with. We have seen this type of collaboration before, where lung cancer patients have the worst possible results for radio-thoracic surgeons, but they are the best possible patients for us, so it becomes a win-win for everyone," Robinson explained.

Next steps in EP radiotherapy ablations

While the results seem hopeful, more research is needed before this type of therapy can become mainstream. Cuculich said it is still a new procedure that may carry serious risks, so operators need to be very careful and do the research in extremely rigorous and methodical way. This means it really needs to be done in randomized controlled trials for a proper comparison. 

Cuculich said the positive results of this study has lead to the announcement of a new prospective, multi-national randomized controlled trial that opened enrollment in early May. The RADIATE VT trial is sponsored by Varian Medical Systems. It will compare redo catheter ablation to cardiac radiation therapy ablation.