Radiofrequency ablation (RF) has changed the lives of thousands of arrhythmia patients. However, its use can also lead to unwanted adverse events that are many times unavoidable, such as phrenic nerve injury and esophageal fistula. The use of cryotherapies has been one approach to lessening these events, though issues still remain with cold application. Recently, a couple of promising approaches to ablating arrhythmic foci have been proposed, and clinical studies are starting to be published. These new therapies are electroporation with pulsed field ablation and stereotactic arrhythmia radioablation (STAR).
Electroporation and Pulsed Field Ablation
What is electroporation? Electroporation involves the use of an electrical field to change the membrane of a cell. The use of the electrical field can permeabilize the membrane and disrupt the layers of the membrane, creating a pore that can allow the introduction of gene therapy or cancer drugs. This type of electroporation is called reversible electroporation, as the cell remains intact and the pore formation is just temporary. This is usually done with unipolar delivery. The electrical field charge used in this situation is about equal to 250 mV.1
Irreversible electroporation uses a higher frequency and is most effective when delivered as bipolar bursts. Cells have difficulty recovering from the pore formation at a higher frequency, and they die because of loss of homeostasis.1 This type of electroporation is used to treat cancerous tumors. It is the use of the higher frequency bipolar bursts that is being proposed as an approach to treatment of arrhythmogenic tissue and as an alternative to RF.
Pulsed field ablation is nonthermal and tissue selective. Myocardial cells are more sensitive to this electrical field because they have a lower threshold for cell damage. The same application seems to spare nerves, arteries, veins, and the esophagus. FARAPULSE Inc. makes a special delivery catheter and generator for this procedure. The majority of work with pulsed field ablation has involved the study of atrial fibrillation (AF).
How does this type of ablation take place? The patient undergoes the standard EP mapping routine to identify and characterize the arrhythmia. They do not require a paralytic agent as the electrical field does not cause muscle contraction. After identifying the target zone, the specialized catheter is introduced and the pulses are delivered. This could take between 20-60 minutes of catheter dwell time in an atrial fibrillation study, but less than 60 seconds of total delivery time.2
Animal and Clinical Studies
Data from animal studies and recent clinical studies are showing results with great potential for this technique. Koruth et al3 reported on a chronic porcine study delivering AF ablation lesions using pulsed field ablation. They demonstrated that nerves and pulmonary veins were spared and the lesions were more durable than the RF lesions.
At the recent AF Symposium 2020, three posters of interest dealt with pulsed field ablation. Jais et al2 presented work with 23 paroxysmal atrial fibrillation patients, demonstrating that 100% of the pulmonary veins were isolated. Late gadolinium-enhanced MRI showed no phrenic nerve or esophageal lesions present post procedure.
Reddy et al4 presented the work from 3 centers with 113 patients undergoing pulsed field ablation for AF. These patients were remapped in 75-90 days and monitored for 1 year. There were events in 1.8%: 1 pericardial tamponade and 1 groin hematoma. An EGD was performed in 56, finding no thermal injury. Sixty patients underwent MRIs, and no PV stenosis was seen. Fifty-one patients reached the 1-year follow-up with no latent safety concerns. Remapping was performed in 92, and the lesions were deemed durable.
Kawamura et al5 presented data on 14 paroxysmal atrial fibrillation patients undergoing pulsed field ablation. These patients were studied 3 months post procedure and vein isolation persisted.
The preliminary data presented here suggests that pulsed field ablation may have great potential to replace some of the RF we are currently performing, with fewer complications.
Radiotherapy for Ablation
Radiotherapy is a treatment modality that has been used for a number of years in the oncology realm to treat solid tumors in the spine, lungs, liver, prostate, and pancreas. More recent treatment diagnoses have included trigeminal neuralgia, AV malformations, and seizures. The ability to precisely target the area of treatment has occurred because of the development of radiosurgery of tumors in the brain and nervous system. The goal in this case is to minimize danger to surrounding tissues while pinpointing areas for treatment. This ability to precisely deliver radiation has led to the proposed use of radiation to target arrhythmic foci in the heart that may be located in hard-to-reach areas or in deep tissue regions.6,7
Radiotherapy is the use of photons from x-ray or gamma rays to cause tissue injury with precision and efficacy. The mechanism of injury to the tissue is not entirely clear. It is thought that the process probably involves injury to the vasculature, followed by tissue hypoxia. This leads to necrosis, apoptotic cells, and cell death. Fibrosis and scar formation follow. The injury may occur over a period of days to months. The use of this technique for the treatment of arrhythmias is known as stereotactic arrhythmia radioablation.6,7
The delivery of radiation to the heart utilizes a robotic arm on a delivery platform that is able to deliver beams from multiple angles. This modern delivery technique is called intensity-modulated radiotherapy (IMRT), and targets a three-dimensional volume. The procedure is performed on an outpatient basis, is noninvasive, does not require anesthesia or sedation, and has no instrumentation except in rare instances. A major concern of this treatment approach is the possible risk to adjacent structures, such as the esophagus, lungs, arteries, and nerves. The long-term side effects are currently not known.6,7
Preprocedural Imaging and Mapping
It is of the utmost importance that the area to be treated is precisely identified. CT and x-ray studies are essential. If the desired treatment area is a scar region, as is often the case in VTs, scar imaging modalities will be ordered. This may include nuclear perfusion imaging, cardiac MRI, CT angiography, detailed transthoracic echo for wall motion data, and electroanatomical mapping from a prior EP study and/or ablation.
Any prior intracardiac mapping and noninvasive body surface mapping is also used. The 12-lead EKG can help identify VT origin. The 12-lead may also be used if the therapeutic target is atrial flutter, PVCs, an accessory pathway location, or an atrial tachycardia.
Finally, the treatment plan is developed. This requires the use of specialized software that identifies not only the target area, but also the proposed lesion volume.
The patient is brought into the treatment room and placed in a supine position and instructed to make only minimal movement. Because respiratory movement is not preventable, the technique of respiratory gating or other motion compensation strategies may be used. This means that treatment delivery is synchronized to a certain point in the respiratory cycle. Another approach may be the use of a tracking type of system where the radiation beam follows a moving target and adjusts accordingly. Such targets could include a radiopaque marker, a temporary pacemaker lead, a stent, or an artificial valve as a reference point.6,7
The procedure is painless and requires no anesthesia. The dose being used for VT cases is about 25 Gy in a single dose. Treatment time could range from 10 to 90 minutes. The patient is observed for a brief time after and then discharged.
The follow-up involves rhythm monitoring as well as adverse event and symptom monitoring. In addition, monitoring for evidence of scar formation will be done with the use of CT, PET, MRI, or noninvasive body surface mapping. Reduction of arrhythmias will occur over several days to several months. A very limited number of patients have been treated thus far, and most of these have been for VT or atrial fibrillation. See the process summary in Table 1.
As this technology has developed, there are other targets that have been proposed, including catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome, ablation of the stellate ganglionic plexus, and renal autonomic denervation for hypertensive patients. As is true with all new technologies, more studies are needed to look at larger populations as well as safety and efficacy. Long-term follow-up is essential, as we know so little at this time.
Animal and Clinical Studies
A report from Robinson et al8 last year discussed the use of radioablation in 19 patients, 17 with VT and 2 with PVCs. Treatment times ranged from 5.4-32.3 minutes. Two patients developed treatment-related serious events in the first 90 days, 1 for heart failure 65 days post treatment, and 1 for pericarditis 80 days post treatment. One patient died 17 days after treatment in a nursing home–related accident. Other post-procedure symptoms included fatigue, hypertension, nausea, dizziness, dyspnea, and pneumonitis. Seventeen of 18 patients had ICDs. The total number of events 6 months prior to treatment was compared to the total 6 months after. Before treatment, a total of 1778 events were captured, compared to 149 in the 6 months after. Use of two antiarrhythmics changed from 59% prior to 12% after. Amiodarone use changed from 47% prior to 12% after. Class 1 agent use changed from 59% to 12%. Three people were able to totally stop the medications. The risks were considered modest and short-term, and the ventricular arrhythmia burden was greatly reduced. The authors were encouraged with their results, and suggest continued research and the gathering of safety and efficacy data.
Zei et al9 reported on the use of stereotactic radioablation on the pulmonary veins. In this canine study, 17 adult canines had markers placed and a computed tomography angiogram of the left atrium was developed along with a treatment plan. Therapy was delivered. There were no complications up to 6 months post procedure, precise circumferential scars were produced, and vein isolation occurred. This animal study points to the potential of radiotherapy in the AF population.
Pulsed field ablation and stereotactic arrhythmia radioablation offer fresh approaches to arrhythmia treatment. Adapting these techniques that have been primarily developed by oncologists to the arrhythmia patient expands the possibilities for safe and effective treatment.
Disclosure: Ms. Moulton has no conflicts of interest to report regarding the content herein.
- Ivey J, Latouche EL, Richards ML, et al. Enhancing irreversible electroporation by manipulating cellular biophysics with a molecular adjuvant. Biophys J. 2017;113:472-480.
- Jais P, et al. Lesion visualization of pulsed field ablation by MRI in an expanded series of PAF patients. Proceedings from the 25th Annual International AF Symposium, January 2020. Poster #37.
- Koruth J, Kuroki K, Iwasawa J, et al. Preclinical evaluation of pulsed field ablation: electrophysiological and histological assessment of thoracic vein isolation. Circ Arrhythm Electrophysiol. 2019;12(12):e007781.
- Reddy V, et al. Lesion durability and safety outcomes of pulsed field ablation in >100 paroxysmal atrial fibrillation patients. Proceedings from the 25th Annual International AF Symposium, January 2020. Poster #19.
- Kawamura I, et al. Do pulsed field ablation lesions regress over time? A quantitative analysis of the PVI level of isolation in the acute and chronic settings. Proceedings from the 25th Annual International AF Symposium, 2020. Poster #54.
- Kim E, Davogustto G, Stevenson WG, John RM. Non-invasive cardiac radiation for ablation of ventricular tachycardia: a new therapeutic paradigm in electrophysiology. Arrhythm Electrophysiol Rev. 2018;7(1):8-10.
- Zei P, Soltys S. Ablative radiotherapy as a noninvasive alternative to catheter ablation for cardiac arrhythmias. Curr Cardiol Rep. 2017;19(9):79.
- Robinson C, Samson PP, Moore KMS, et al. Phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia. Circulation. 2019;139(3):313-321.
- Zei P, Wong D, Gardner E, Fogarty T, Maguire P. Safety and efficacy of stereotactic radioablation targeting pulmonary vein tissues in an experimental model. Heart Rhythm. 2018;15(9):1420-1427.