By Joshua Moss, MD

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

Dr. Moss reports he is a consultant for Abbott and Biosense Webster.

SYNOPSIS: In 19 patients with treatment-refractory episodes of ventricular tachycardia or frequent premature ventricular contractions, stereotactic body radiation therapy was highly effective at reducing arrhythmia burden without acute toxicity.

SOURCE: Robinson CG, Samson PP, Moore KMS, et al. Phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia. Circulation 2018. Published online Nov. 10, 2018. Available at: https://bit.ly/2TKIq4d. Accessed Dec. 5, 2018.

The field of cardiac electrophysiology has advanced rapidly regarding ablation of cardiac arrhythmias, albeit with little change to the types of ablation energy delivered. Management of patients with ventricular tachycardia (VT) in the setting of myocardial scarring remains a challenge. Treatment failures are common when scarring is extensive or critical areas are inaccessible with available technology. Ablation procedures for VT also may take many hours to complete. Complications, while infrequent, can be serious.

Robinson et al sought to further assess the safety and efficacy of entirely noninvasive techniques for both identifying arrhythmia substrate and delivering ablation energy, expanding upon their previously published case series.1 In a prospective, single-arm, Phase I/II trial conducted at a single center, the authors used a synthesis of imaging studies and body surface-based electrophysiological mapping to guide treatment with stereotactic body radiotherapy (SBRT). Patients received a single dose of 25 Gy via SBRT to target areas of ventricular scarring determined to harbor the re-entrant VT circuit. Follow-up, including serial chest CTs, was performed at predetermined intervals until 12 months. The primary safety endpoint was defined as the rate of serious adverse events within 90 days (grade 3 toxicity requiring hospitalization or any grade 4 or 5 toxicity). The primary efficacy endpoint, following a six-week blanking period, was defined as reduction in the number of implantable cardioverter defibrillator (ICD) treatments or 24-hour premature ventricular contraction (PVC) burden between the six-month periods before and after SBRT.

Nineteen patients (17 male) with a median age of 66 years were enrolled. To be eligible, subjects had to have experienced at least three episodes of sustained VT (17 of 19 patients) or cardiomyopathy related to PVCs (2 of 19) and to have failed at least one antiarrhythmic medication and one catheter ablation procedure. Eleven patients had an ischemic cardiomyopathy. Median baseline ejection fraction (EF) was 25%. Patients were excluded if they had received prior radiotherapy, had New York Heart Association class IV heart failure, or were deemed unlikely to live 12 months even in the absence of VT. Median treatment time for delivery of SBRT was 15.3 minutes (range, 5.4-32.3).

All but one patient experienced a significant reduction in ventricular tachyarrhythmia or PVC burden, with a reduction of at least 75% in 17 of 19 patients. Excluding the six-week post-SBRT blanking period, the median number of VT episodes decreased from 119 in the six-month period pretreatment to three in the six-month period post-treatment. ICD therapies also declined significantly, from a median of four ICD shocks to zero and 81 antitachycardia pacing therapies to 3.5.

There was no acute toxicity attributed to the SBRT. Serious adverse events up to 90 days included one instance each of pericarditis requiring corticosteroids, heart failure requiring hospitalization, nausea/vomiting, and transaminitis. Transient fatigue and hypotension requiring adjustment of antihypertensive medications were common. There was one patient death at 17 days after treatment that was attributed to a nursing home accident unrelated to the study. The authors concluded that in patients with treatment-refractory episodes of VT or frequent PVCs, stereotactic body radiation therapy reduced arrhythmia burden significantly and without acute toxicity.

COMMENTARY

This study is an extension of the smaller case series of five patients published by the same group last year, a series that generated considerable excitement as well as many questions. As a prospective Phase I/II trial, the goal was to evaluate both efficacy and safety endpoints in preparation for a multicenter trial scheduled to start in 2019. As with the initial case series, SBRT was effective in achieving dramatic reductions in VT burden. The authors also demonstrated reduction in antiarrhythmic drug use, most notably amiodarone. Importantly, there was only one serious adverse event in the first 90 days after therapy that was believed to probably be related to therapy — an episode of pericarditis at day 80 that improved with steroid therapy. Lower-grade adverse events included pericardial effusions and radiation pneumonitis.

It is interesting that two patients were included with high PVC burden and cardiomyopathy (rather than sustained VT), an indication for SBRT not pursued in the original case series. In those patients, 24-hour PVC burden declined from 24% to 2% and from 26% to 9%, respectively. There was an attendant improvement in EF (13% and 8%, respectively). Catheter ablation for PVCs often can be performed with a high rate of success and low risk of complications, but there are some common areas of PVC origin that are relatively inaccessible to catheters; novel techniques such as SBRT are needed. Finally, both the patient experience and improvements in quality of life are noteworthy. SBRT therapy lasted a median of 15 minutes, after which patients could simply go home. In contrast, complex VT ablation procedures can involve a day-long experience on a procedure table, particularly when addressing arrhythmias refractory to other therapies, and one or more nights in the hospital. After the SBRT procedure, patients reported significant improvement in perceived health change and social functioning categories on quality of life surveys, with no significant decline in any domain.

It is important to remember that this therapy remains investigational, and results have not yet been reproduced outside the original center. Longer-term adverse effects of SBRT for this indication also remain unknown. However, the reproducibility and sustainability of the results in this larger population are reassuring and should increase interest in this technology as part of research protocols in high-volume tertiary care medical centers.

Overall, the use of SBRT for refractory VT and PVCs shows great promise and may prove to be an exciting, safe, and effective treatment modality in the management of this challenging patient population.

REFERENCE

  1. Cuculich PS, Schill MR1, Kashani R, et al. Noninvasive cardiac radiation for ablation of ventricular tachycardia. N Engl J Med 2017;377:2325-2336.