Given that we are at the stage where pulsed field ablation (PFA) is fully emerging in the field of clinical cardiac electrophysiology, it is imperative to discuss the place of PFA in the discipline, including its main advantages—both scientific and practical. PFA can be used in a number of different ways, but its most valuable benefit is best illustrated by catheter ablation of atrial fibrillation (AF), and it is important to put it in context.
First, atrial fibrillation is a huge problem, affecting more than 30 million new patients worldwide each year. Second, atrial fibrillation is a solvable problem, and catheter ablation is considered by many to be the most effective treatment. Third, AF ablation has its own problems, with 500,000 cases per year, and a less than ideal safety profile. Thermal ablation—such as radio frequency (RF), laser, ultrasound, microwave, and cryoablation—affects tissue that is too hot or too cold to die. This can include nearby structures or tissues outside the heart, leading to rare unintended complications. It is here that PFA is very different.
The way PFA is damaged is metabolism. It interferes with key metabolic functions that maintain cell survival. The strong electric field generated during PFA causes the cell membrane to open, a process called electroporation. Temporary membrane failure puts incredible strain on the cell’s metabolic machinery. Once the electric field collapses, the cell membrane quickly reseals and the cell may continue its normal activities. Cardiac tissue in and around PFA lesions has observable blood vessels, nerves, and endothelium, all of which appear to be unaffected by the disappearance of target cardiomyocytes.
The practical benefit of preserving tissue structure and blood supply is rapid tissue healing – usually within 2-3 weeks. In contrast, radiofrequency ablation requires 4-6 weeks to heal, along with regeneration of the blood supply, tissue factor reconstitution, and prolonged inflammation. Because cardiomyocytes are very sensitive to PFA damage patterns compared to most other tissue types in the body, this means we can more safely ablate heart tissue close to structures such as the esophagus, phrenic nerve, lungs, and blood vessels. It is important to realize that this favorable contingency is just biology and not some special tunable property of the PFA waveform.
I like to say that PFA is easy. At a minimum, only a defibrillator and a diagnostic catheter are required. However, detailed and practical PFA techniques require more work. Contemporary PFA technologies under development utilize short pulses of kilovolt-scale microsecond or nanosecond pulses delivered through one or more electrodes to target tissue. There are some variations on the teleporter: flowers, baskets, rings, and sticks. Current waveforms and delivery strategies have extensive variability. I expect the entire industry will eventually focus on a PFA-like formulation that makes sense for most cardiac ablation applications. I think we’ll be successful when PFA becomes tedious and out of sight for the operator so we can focus on treating the patient. After all, PFA is just an alternative to creating a therapeutic scar in the heart.
The cornerstone of AF ablation is anatomical pulmonary vein isolation (PVI), which alters the source of energy. Single-shot PVI devices that mimic the cryoballoon workflow appear to be emerging as an emerging clinical strategy. Most market leaders in our field have invested hundreds of millions of dollars in their own single-shot PFA tools. Recent data show that PVI has a single-procedure success rate of over 90%. The second strategy involves tools that can be implemented in the more traditional point-by-point approach found in radiofrequency ablation catheter workflows. Here, linear lesions are created by sequential ablation to encircle the target vein or create any of the various lesions that can be produced with conventional radiofrequency catheters.
As the field of cardiac PFA develops, there may be a wide range of therapeutic strategies that can be optimized for each intended use. The variables of PFA waveform development are much more complex than traditional RF applications. These include electrode geometry, peak voltage, pulse duration, pulse repetition, pulse repetition pattern and/or pulse phase. Understanding target tissue physiology is critical to success, as tissue cell size, shape, site orientation, cell membrane composition, cellular energetics, pH, extracellular environment, and temperature can all affect results. The potential complexity and variety of drug delivery strategies make direct comparison of the results of different catheter waveform therapy strategies nearly impossible. That said, PFA can be equally effective using different wave configurations and catheter configurations.
The key to PFA’s true value may lie in how the technology can be adapted for more personalized treatment strategies and integrated into contemporary 3D mapping applications. PFA lesion volumes and contours follow well-defined and predictable electromagnetic rules, unlike radiofrequency ablation, where the prediction of heat transfer is much more complex. Because the PFA field is more predictable, physicians can plan procedures with greater confidence and tailor treatment to ablate only the target tissue, while preserving cardiac tissue not involved in the arrhythmia. Powerful mapping techniques can now visualize global activation patterns in complex arrhythmias to reveal fundamental electrophysiological properties of heart disease. We have long recognized the presence of heterogeneous conduction abnormalities on diseased tissue, but measurements outside the research laboratory are often difficult or impractical.
Technology has advanced to the point where we can measure functional electrophysiology. Constellation of previously unseen patterns and characteristics is emerging, showing growing promise in our struggle to understand complex arrhythmias. There are techniques that analyze multiple wavefronts of chamber activation and identify areas of the heart that can contribute to the maintenance of arrhythmias such as atrial flutter or AF. It is innovations like this that I believe are needed for a point-by-point ablation technique that can produce predictable lesions. It was an exciting moment, like Galileo pointing his telescope to the sky for the first time. In the future, 3D electroanatomical maps of any arrhythmia can be quickly created, and treatment strategies can be planned based on individualized knowledge. This is where integration with PFA technology can have significant advantages in delivering tailored treatments, with significant improvements in reliability and workflow.
Photo: Narongrit Doungmanee
