Most American electrophysiologists have not had a chance to try pulsed field ablation (PFA). All we knew about PFA was the enthusiasm of our European colleagues. The European Society of Cardiology congress brought us some evidence. We learned the results of the ADVENT randomized controlled trial comparing PFA to standard thermal ablation for patients with atrial fibrillation (AF). The results mismatched the enthusiasm of our colleagues.
The US-based ADVENT trial was designed with approval from the Food and Drug Administration (FDA) for regulatory clearance of PFA to treat AF.
PFA is novel. It stops cell-to-cell conduction by delivering electricity and creating pores in cell membranes. This strategy is promoted as safer because it promises to select only cardiac cells, which should limit damage to the esophagus and phrenic nerves. It is also fast; European registry studies report procedure times well under an hour.
The ADVENT Trial
In ADVENT, slightly more than 600 patients with paroxysmal AF were randomly assigned to ablation (pulmonary vein isolation) using thermal energy (radiofrequency or cryoballoon) or pulsed field ablation.
The primary efficacy endpoint was freedom from a composite of initial procedural failure, atrial tachyarrhythmia after a 3-month blanking period, use of antiarrhythmic drug, cardioversion, or repeat ablation. The primary safety endpoint included acute or chronic device- or -procedure-related serious adverse events.
The authors used a complicated statistical design, the most notable being a Bayesian analytic method and non-inferiority tests for both the efficacy and safety endpoints.
The Results for Pulsed Field Ablation
At one year, 73.3% of patients in the PFA arm avoided a primary endpoint vs 71.3% in the thermal energy group. This led to a > 99.9% probability of non-inferiority. PFA did not achieve superiority.
A primary safety endpoint occurred in 2.1% of patients in the PFA group vs 1.5% in the thermal energy group. This also met the bar for noninferiority.
Total procedure time was shorter in the PFA group (105 vs 123 minutes). An additional catheter ablation in the right atrium for atrial flutter was done in 23% vs 28% of patients in the PFA vs thermal groups, respectively.
Atrial esophageal fistula and pulmonary vein stenosis did not occur in either group. Phrenic nerve injury and paralysis did occur in both groups — four patients in the PFA group, all with resolution, and seven patients in the thermal arm, five with resolution.
Serious adverse events occurred in 51 vs 52 patients in the PFA and thermal groups, respectively. Notably, two patients in the PFA arm had pericardial tamponade, one resulting in death vs no tamponade events in the thermal group.
I will start with the obvious. American electrophysiologists have had a year or more to hear the enthusiasm of their European colleagues, but the evidence from ADVENT is quite underwhelming.
Ablation success rates were similar in both groups and the ADVENT authors declared PFA noninferior to standard ablation. That is hardly a reason for enthusiasm, especially since their chosen margin of noninferiority was extremely permissive (15% in absolute terms). PFA has done nothing to break our 20-year plateau in AF ablation success rates, which hover around 75%.
While rates of serious adverse events were similar in both arms, the only two cases of pericardial tamponade, one with death, were in the PFA arm. What’s more, PFA is purported to be cardio-selective, but there were cases of phrenic nerve injury with PFA.
A small number of patients in each group had brain MRI imaging to assess for silent cerebral lesions. This is an important data point because of the intense bubble formation created during PFA in the left atrium. Three of 33 patients had silent cerebral lesions in the PFA arm vs zero of 37 patients in the thermal arm. Those numbers are too small to make conclusions, but surely, we should have more data on brain imaging.
Another downside of PFA, not mentioned in the presentation, is that if a patient with AF is found to have another arrhythmia, such as atrial flutter or supraventricular tachycardia, the operator must open another catheter. This would increase costs of the procedure. More than 20% of patients in both groups required additional ablation for atrial flutter.
I spoke with a number of European colleagues about PFA here at ESC. They emphasized that it’s a faster, simpler procedure. Average PFA procedure time was 100 minutes in ADVENT, but every experienced operator I spoke with said procedure times will drop as US doctors gain experience. These experts also emphasized that technically simpler procedures may increase safety in the hands of low-volume operators — who are numerous in the US.
With any new technology, it is important to recognize that early studies like ADVENT use first-generation tools. Many device companies are developing PFA devices, and it seems likely that electrophysiologists will soon have better devices to deliver PFA.
In sum, the actual data on PFA, acquired from the most experienced experts in the US, is underwhelming. It’s likely to be good enough to pass the FDA bar, but I will be a slow adopter. And if I had AF that required ablation today, I’d ask the operator to use a thermal ablation technique.
John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence.
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Cite this: Pulsed Field Ablation Noninferior but Underwhelming in ADVENT - Medscape - Aug 28, 2023.