Reaching for the STARs in the EP Lab: Stereotactic Arrhythmia Radioablation

Despite progressive advances over the past 30 years in radiofrequency (RF) catheter ablation for cardiac arrhythmias, several limitations remain. These limitations include the risks inherent to the invasive nature of the procedure, the inability to easily reach certain cardiac structures including the left ventricular summit and midmyocardial left ventricle, and the potential for damage to collateral structures such as the AV node, esophagus, and phrenic nerve. For these reasons, there have been continued efforts to figure out how to ablate cardiac structures using noninvasive techniques. Previous work using high intensity focused ultrasound (HIFU) appeared promising. However, the challenge of creating a contiguous lesion without gaps has limited its adoption for cardiac ablation.¹

 

The use of external radiation to ablate cardiac tissue now appears to be gaining momentum. A review article on the topic, recently published online by one of the leaders in the field, Dr. Paul Zei², nicely summarizes the history and current status of the approach. Radiotherapy using ionizing radiation delivered to specific targets is a common treatment for solid tumors. Historically, radiation therapy (XRT) has involved the delivery of intensity-modulated radiotherapy with intermittent dosing over several weeks. It is effective in this way because the normal tissue recovers better than the malignant tissue between treatments. A major advance in XRT is the ability to deliver convergent beams to tissue that results in stereotactic precision, allowing for very high single doses to be delivered to the tumor while avoiding surrounding tissue. For example, using computer-optimized three-dimensional “dose sculpting”, stereotactic ablative radiotherapy (SABR) can cure a front lobe brain tumor in a child while avoiding the optic nerves. These advances have allowed for the development of a technique to treat arrhythmias using the same type of therapy, and has been referred to as stereotactic arrhythmia radioablation (STAR). 

 

An obvious challenge of using radiotherapy to attack a cardiac target rather than a brain tumor is motion. Although cardiac contraction is part of the problem, cardiac displacement during respiration results in even more movement of the heart within the chest. Methods to address this problem include using an image guidance system to track a cardiac fiducial point, such as a cardiac valve or temporary pacing wire, and then deliver therapy only when the heart is in the therapy window, or deliver therapy continuously while synchronously redirecting the beams in real time with movement of the target. For example, the CyberKnife (Accuray Inc.) is an image-guided stereotactic radiosurgery system used to treat solid tumors. Another limitation to STAR is identification of the target responsible for the arrhythmia before treatment. To avoid adding an invasive mapping component to radiotherapy for ablation, current efforts involve noninvasive body surface mapping to identify ablation targets.

 

The impact and mechanism of injury using radiotherapy is quite different than when using RF energy, in that the effects are delayed and appear to be based on microvascular injury and apoptosis. There are also safety concerns with STAR, including injury to nearby structures and premature atherosclerosis. Despite these limitations, however, groups have already published successful ablation of the AV junction in animals using external radioablation³, and using carbon particle beams rather than protons.⁴ Dr. Zei claims in his recent review article that radiotherapy has been used successfully to achieve electrical isolation of a pulmonary vein in an animal.²

 

Imagine an EP lab where patients come in wearing their street clothes, lie down in a STAR gantry, and leave after 15 minutes, cured of their heart rhythm disorder. It seems plausible. At this time, there are two groups enrolling patients in approved human trials in the U.S. using radiotherapy to treat arrhythmias. Early results from the ENCORE-VT trial, a protocol that is enrolling patients with ventricular tachycardia at Washington University and is being led partly by Dr. Phillip Cuculich as the principal electrophysiologist, are expected to be published soon in a major medical journal.