By Joshua D. Moss, MD

Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco

Dr. Moss reports no financial relationships relevant to this field of study.

SYNOPSIS: In five patients with recurrent ventricular tachycardia refractory to conventional therapies, relatively short treatments with electrophysiology-guided stereotactic body radiation therapy were highly effective at reducing arrhythmia burden.

SOURCE: Cuculich PS, Schill MR, Kashani R, et al. Noninvasive cardiac radiation for ablation of ventricular tachycardia. N Engl J Med 2017;377:2325-2336.

Although catheter mapping and ablation techniques advance, ventricular tachycardia (VT) remains a difficult problem to manage in many patients with cardiomyopathy. Arrhythmogenic substrate that is mid-myocardial and not easily targeted with radiofrequency energy delivered from either the endocardial or epicardial surface of the heart poses a particular challenge. Additionally, catheter ablation procedures often take many hours to complete, and complications, while infrequent, can be serious or life-threatening.

Cuculich et al sought to demonstrate an entirely noninvasive technique for both identifying arrhythmogenic substrate and delivering ablation energy to eliminate refractory VT. To identify target areas for ablation, patients underwent multielectrode body-surface electrocardiography using a 256-electrode vest while VT was induced via noninvasive programmed stimulation (NIPS) using their existing implantable cardioverter defibrillators (ICD). The electrocardiographic data, combined with chest CT imaging, were used to identify sites of earliest electrical activation during VT (the “exit sites”). Additionally, single-photon emission CT or MRI was used to identify areas of anatomic scarring. A volumetric target for ablation was identified, targeting the exit site of the VT and the full myocardial thickness of any associated ventricular scar. Patients underwent a specialized planning CT scan to expand the target ablation area, accounting for respiratory and cardiac motion as well as uncertainty in radiation delivery. Once an electrophysiologist and radiation oncologist determined the planned target volume, a single total dose of 25 Gy was delivered using a stereotactic body radiation therapy (SBRT) device, an off-label clinical use.

During an eight-month period, nine patients were evaluated for this novel therapy, and five underwent treatment. Of those five, the mean left ventricular ejection fraction was 23%, all demonstrated New York Heart Association class III or IV heart failure symptoms, all were taking multiple antiarrhythmic drugs, and three had failed prior invasive catheter ablation. Patients experienced between five and 4,312 VT episodes in the three months prior to SBRT (6,577 total episodes for all five patients). The actual radiation treatment required only 11-18 minutes and targeted between 17 and 81 mL of tissue. Patients left the hospital one to two days after treatment. The authors instituted a six-week “blanking period” after radiation therapy to account for expected arrhythmias arising from post-ablation inflammation. One elderly patient with severe cardiomyopathy, a very high VT burden, atrial fibrillation, and contraindications to anticoagulation suffered a fatal stroke three weeks after treatment. In the remaining four patients, there were four episodes of VT in 46 patient-months after the six-week blanking period, a 99.9% reduction in arrhythmia burden from baseline. Only one ICD shock was delivered during that follow-up period, compared with 55 shocks prior to treatment.

COMMENTARY

Although small, this study is remarkable in several ways. First, it represents a completely novel approach to the treatment of VT that relies on neither antiarrhythmic drugs (and their associated toxicities) nor invasive catheter mapping and ablation (with lengthy procedure times, limitations in delivering transmural energy, and risk of acute complications). After careful, noninvasive, and relatively low-risk planning procedures, the actual radiation therapy required an average of < 15 minutes. The reduction in arrhythmia burden far exceeded nearly all prior studies of invasive catheter ablation for VT, although to be fair, the actual recurrence rate was technically 50%. Of the four patients who survived past the six-week blanking period and onward to one year of follow-up, one experienced three episodes of recurrent VT during follow-up (compared to 30 in the three months pre-treatment), and another patient experienced one episode during follow-up (compared to five in the three months pre-treatment). Nevertheless, all patients discontinued antiarrhythmic medication, with one patient restarting amiodarone at nine months.

The authors wisely cautioned against considering the procedure suitable for clinical use based on these initial data alone. Serial CT scans at three months showed inflammatory changes in the lung tissue adjacent to the target ablation area, although there was near-complete resolution by 12 months. That said, late toxic effects to the heart and adjacent structures from high-dose focal SBRT are feasible and will require longer-term follow-up in a larger study population to fully assess. The one patient who suffered a fatal stroke three weeks after radiation treatment presented with multiple risk factors for thromboembolism, including atrial fibrillation without ongoing anticoagulation, but an unanticipated risk of SBRT cannot be ruled out completely.

For now, this procedure likely will be reserved for participants in research trials at limited centers or for compassionate use. However, with further refinement and study, noninvasive cardiac radiation carries the potential to represent a true paradigm shift in the treatment of refractory ventricular tachycardia.