Key Points:
– Pulsed field ablation (PFA) is a novel ablation technology which utilizes electrical pulses to deliver irreversible electroporation and induce thermal cardiac cell death and has shown high cardiac tissue selectivity and safety in preclinical data.
-Over 1 year of follow-up, treatment with PFA to achieve pulmonary vein isolation, achieved freedom from atrial arrhythmias in up to two-thirds of patients.
-Pulse field ablation appears to have an excellent safety profile with only one adverse event occurring in each of the two patient cohorts, for an adverse event rate of 0.7%.
-Patients with both paroxysmal and persistent AF had significant and meaningful improvements in quality of life following their index ablation.
Catheter ablation is well established as an effective and safe modality for the treatment of patients with symptomatic, atrial fibrillation who have failed antiarrhythmic therapy. More recent clinical data has shown that utilization of catheter ablation relatively early in the course of paroxysmal atrial fibrillation, can also positively influence the progression of disease, particularly to more persistent phenotypes. Current ablation energies are thermal based, and carry risks of adverse injury to structures such as the esophagus, phrenic nerve and pulmonary ostia. Pulsed field ablation (PFA) is a novel ablation technology which utilizes electrical pulses to deliver irreversible electroporation and induce thermal cardiac cell death. Preclinical data has shown that PFA is highly selective in ablating cardiac tissue while avoiding damage to nearby structures surrounding the pulmonary veins. In a late-breaking presentation at the ACC.23/WCC in New Orleans today, Dr. Atul Verma (McGill University Health Centre, Montreal, Canada) and his team presented their study: “Pulsed Field Ablation Treatment In Paroxysmal And Persistent Atrial Fibrillation Patients: Acute And Long-term Outcomes From The Pulsed AF Pivotal Trial”.
The PULSED AF pivotal trial (NCT04198701) was a prospective, multicenter, global, nonrandomized, paired single-arm clinical trial and the first to evaluate PFA for the treatment of atrial fibrillation. This study conducted across 41 centers in nine (9) countries, with 67 operators aimed to evaluate the 12-month effectiveness and safety of the pulsed field ablation system in a population of patients with paroxysmal or persistent symptomatic AF. After a roll-in period patients with recurrent, symptomatic, drug refractory AF with both paroxysmal (n = 150) and persistent (n = 150) AF were treated with a PFA system with the aim of achieving pulmonary vein isolation (PVI). The mean age in the paroxysmal and persistent cohorts were 63 and 66 years respectively, with majority being male (64% and 75% respectively). In total, 146 of 150 (97%) patients with paroxysmal AF and 141 of 150 (94%) patients with persistent AF completed follow-up. Acute pulmonary vein isolation was achieved in 100% of patients in both cohorts. The mean device left atrial dwell time (mins), (i.e.) the time spent in the left atrium with catheters to deliver applications, was ~60mins, inclusive of a mandatory 20min wait time per protocol.
The study had a very rigorous post PVI monitoring protocol over one year. All patients were monitored with weekly and symptomatic trans-telephonic monitoring; 3-, 6-, and 12-month ECG’s; and 6- and 12-month 24-hour Holter monitoring. The primary efficacy outcome was the freedom from all atrial arrhythmias through 12 months, excluding an initial 3-month blanking period, which was seen in in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The core lab adjudicated primary safety endpoint of freedom from a composite of serious procedure and device-related adverse events occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF study cohorts. Post ablation changes in quality of life by the AFEQT score improved by a mean of 29.4 (95% CI, 25.8–33.1) and 29.0 (95% CI, 25.5–32.5) points from baseline to 12 months in paroxysmal and persistent cohorts. As measured by EQ-5D-5L score, there was improvement 0.05 points (95% CI, 0.02–0.08) in paroxysmal AF and 0.06 points (95% CI, 0.04–0.09) in patients with persistent AF. These numerical differences in QoL scores are thought to be meaningful changes. Among the 45 patients who were screened with cerebral MRI for post procedural silent cerebral lesions, 4 (8.9%) had a new, postprocedural silent cerebral lesion.
This novel PFA system technology has generated significant enthusiasm and excitement for the treatment of patients with atrial fibrillation. This study shows that with the use of a novel technology, operators were able to achieve acute success safely, speaking to the learning curve of this system. Additionally, procedural times were quite nominally shorter than traditionally seen in other thermal application modalities. Although the early efficacy and safety data is promising, there are several limitations of the study with some early clinical data worth acknowledging. One of the major limitations of this study was the lack of a control group. Given the very low rates of adverse events related to catheter ablation for AF, larger studies will be prudent in the future to provide more definite information on the safety profile of this new technology. There was no long term phrenic nerve injury noted in this study, but recorded instances of phrenic nerve stunning which quickly resolved. Although the risk of esophageal injury is significantly lower with this technology, this would not have been definitively addressed in this PVI focused study. In addition, early case reports of coronary vasospasm related to PFA will require vigilance, although no episodes were noted in this clinical study.
This study was funded by Medtronic. For additional reading, the study is simultaneously published online in Circulation.
When discussing the clinical implications of the study at ACC.23/WCC, Dr. Verma stated that: “I think this (PFA) really is a paradigm shift, given its safety and efficacy.” He did however, caution that “comparative studies will be necessary.”
References
Bradley CJ, Haines DE. Pulsed field ablation for pulmonary vein isolation in the treatment of atrial fibrillation. J Cardiovasc Electrophysiol. 2020 Aug;31(8):2136-2147. doi: 10.1111/jce.14414. Epub 2020 May 16. PMID: 32107812.
Reddy VY, Petru J, Funasako M, Kopriva K, Hala P, Chovanec M, Janotka M, Kralovec S, Neuzil P. Coronary Arterial Spasm During Pulsed Field Ablation to Treat Atrial Fibrillation. Circulation. 2022 Dec 13;146(24):1808-1819. doi: 10.1161/CIRCULATIONAHA.122.061497. Epub 2022 Sep 22. PMID: 36134574.
