Noninvasive Proton Beam Therapy Safe for VT Ablation: Early Series

Proton beam therapy to target ventricular tachycardia (VT) refractory to medical therapy and prior catheter ablation appears to provide some relief for patients with limited treatment options, according to results of an early feasibility study.

The therapy, which noninvasively delivers charged particles to heart, was successfully performed in a small cohort of patients with advanced cardiomyopathy and recurrent arrhythmias, with no evidence of harm to the heart or other organs, Konstantinos C. Siontis, MD (Mayo Clinic, Rochester, MN), and colleagues report in Heart Rhythm. The results were presented this week at Heart Rhythm 2026.

“We were able to enroll patients and successfully plan and deliver treatment in seven humans, building upon the extensive preclinical work that has been done here at the Mayo Clinic,” Siontis told TCTMD. “We did not observe any probable or definite treatment-related toxicities that could be related to the proton beam therapy. Certainly, we’re quite happy with that.”

The predecessor of proton beam therapy is photon beam radioablation, which is used by radiation oncologists for the treatment of different cancers and has been investigated as a treatment for refractory VT, but proton beam therapy is a little more advanced, said Siontis.

“The radiation modality is a charged particle which is emitted into the heart tissue, or whatever the target might be, with a higher accuracy compared to the photons,” he said. “There’s a biophysical property of the protons that allows them to be targeted into the area we want to ablate while minimizing the radiation to the surrounding tissue. We know from cancer care that the protons have more of a sparing effect compared with conventional radiation, such as with photons.”

In this way, electrophysiologists can focus the energy on the VT substrate while sparing the nontargeted myocardium, coronary arteries, and other noncardiac structures, Siontis added.

Lots of Case Planning

The first-in-human study included seven patients (mean age 68 years; six male) who completed treatment. Of these, four had nonischemic cardiomyopathy, one had ischemic cardiomyopathy, and two had mixed disease. Median LVEF at baseline was 26%. Three patients had biventricular implantable cardioverter-defibrillator (ICD) devices, including two with high-grade atrioventricular block at baseline. Five of the patients had undergone two or more catheter ablations in the past, and six patients were treated with amiodarone with or without mexiletine for several weeks before proton beam therapy. All patients had breakthrough VT after their last ablation procedure despite drug therapy.

The target for treatment was based on information from cardiac imaging, ECG, and electrophysiologic studies. All patients underwent late gadolinium-enhanced MRI with information from echocardiography, and as available, from nuclear perfusion, CT, and voltage mapping supplementing the MRI to define the substrate.

To plan radiotherapy, patients underwent a CT-based planning simulation to highlight the target for radioablation and all cardiac substructures. All nearby organs at risk (esophagus, trachea, lungs, spinal cord, and nontarget LV myocardium, among others) were outlined on CT to spare them excessive radiation exposure during the procedure. Proton irradiation was delivered using the Probeat-V Proton Beam Therapy System (Hitachi), and a median of 1 VT morphologies were targeted per patient.

All of these patients had failed everything else that we’d done for them. Konstantinos Siontis  

“It is a very thorough treatment planning approach that we follow, and that we extrapolate from what the radiation oncologists do,” said Siontis. “When we do our treatment planning, we can plan the exact dose that each of those [organs at risk] will receive. We have certain restrictions and limits for how much we can radiate each of those structures and we have adopted a very restrictive approach, especially as we’re starting this line of work, to protect those tissues as much as possible, realizing that there might be an adverse effect by targeting those areas with high doses.”

During a median follow-up of 514 days, six of the seven patients had at least one VT event. However, VT became less frequent in five of six patients. The rate of VT declined from 7.24 events per patient-month in the 3 months before treatment to 1.52 events per patient-month during follow-up. Of the 152 sustained VT events in the 3 months prior to radiotherapy, 6.6% were treated with ICD shock, 82.2% with antitachycardia pacing (ATP), and 11.2% with monitored. In the 17.1 months after treatment, there were 162 VT events, with 6.8% treated with shock, 91.3% with ATP, and 1.9% with monitoring.

“The VT was very challenging and all of these patients had failed everything else that we’d done for them,” said Siontis. “They did have recurrences, but what is important to note and emphasize is that the burden of VT and the phenotype of VT improved significantly where, in most of the patients, VT became occasionally asymptomatic and ATP-terminated as opposed to having shocks and having a significant impact on their quality of life.”

Delayed Treatment Effect

Interestingly, the treatment effect was not immediate in some patients, suggesting that the mechanism of action may be the induction of progressive necrosis and apoptosis in the cardiac tissue. At the end of 2 years, three patients had died and two had a heart transplant. The two patients who survived to 2 years had infrequent VT breakthroughs and were managed with amiodarone. Given the advanced cardiomyopathy and burden of VT at baseline, these clinical outcomes would be expected.

“By definition, we wanted to include the most advanced patients, the highest-risk patients, who had run out of other conventional options,” said Siontis.

At the moment, photon-based radioablation is more scalable and is being tested in the ongoing RADIATE-VT study. While proton beam radioablation has advantages, including the use of lower doses of radiation, the technology requires specialized infrastructure only available at selected centers.

To TCTMD, Siontis said they have learned from this initial series and will be able to better refine the treatment with gating techniques to correct for motion uncertainties that are introduced when noninvasively targeting a moving target.

If the technology proves viable, researchers don’t imagine proton beam therapy will replace catheter ablation, but it could be used to compliment it, particularly in patients who have either not responded to or are not candidates for the more invasive procedure.